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The 150 most important questions in cancer research and clinical oncology series: questions 94–101

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Cancer Communications

Cancer Communications volume  38 , Article number:  69 ( 2018 ) Cite this article

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Since the beginning of 2017, Cancer Communications (former title: Chinese Journal of Cancer ) has published a series of important questions regarding cancer research and clinical oncology, to provide an enhanced stimulus for cancer research, and to accelerate collaborations between institutions and investigators. In this edition, the following 8 valuable questions are presented. Question 94. The origin of tumors: time for a new paradigm? Question 95. How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma? Question 96. Can we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor? Question 97. What are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction? Question 98. Is high local concentration of metformin essential for its anti-cancer activity? Question 99. How can we monitor the emergence of cancer cells anywhere in the body through plasma testing? Question 100. Can phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells? Question 101. Is cell migration a selectable trait in the natural evolution of carcinoma?

Until now, the battle against cancer is still ongoing, but there are also ongoing discoveries being made. Milestones in cancer research and treatments are being achieved every year; at a quicker pace, as compared to decades ago. Likewise, some cancers that were considered incurable are now partly curable, lives that could not be saved are now being saved, and for those with yet little options, they are now having best-supporting care. With an objective to promote worldwide cancer research and even accelerate inter-countries collaborations, since the beginning of 2017, Cancer Communications (former title: Chinese Journal of Cancer ) has launched a program of publishing 150 most important questions in cancer research and clinical oncology [ 1 ]. We are providing a platform for researchers to freely voice-out their novel ideas, and propositions to enhance the communications on how and where our focus should be placed [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. In this edition, 8 valuable and inspiring questions, Question 94–101, from highly distinguished professionals from different parts of the world are presented. If you have any novel proposition(s) and Question(s), please feel free to contact Ms. Ji Ruan via email: [email protected].

Question 94: The origin of tumors: time for a new paradigm?

Background and implications.

“There is no worse blind man than the one who doesn’t want to see. There is no worse deaf man than the one who doesn’t want to hear. And there is no worse madman than the one who doesn’t want to understand.” —Ancient Proverb

In the past half-century, cancer biologists have focused on a dogma in which cancer was viewed as a proliferative disease due to mechanisms that activate genes (oncogenes) to promote cell proliferation or inactivate genes (tumor suppressor genes) to suppress tumor growth. In retrospect, these concepts were established based on functional selections, by using tissue culture (largely mouse NIH 3T3 cells) for the selection of transformed foci at the time when we knew virtually nothing about the human genome [ 14 ]. However, it is very difficult to use these genes individually or in combinations to transform primary human cells. Further, the simplified view of uncontrolled proliferation cannot explain the tumor as being a malignant organ or a teratoma, as observed by pathologists over centuries. Recently, the cancer genomic atlas project has revealed a wide variety of genetic alterations ranging from no mutation to multiple chromosomal deletions or fragmentations, which make the identification of cancer driver mutations very challenging in a background of such a massive genomic rearrangement. Paradoxically, this increase the evidences demonstrating that the oncogenic mutations are commonly found in many normal tissues, further challenging the dogma that genetic alteration is the primary driver of this disease.

Logically, the birth of a tumor should undergo an embryonic-like development at the beginning, similar to that of a human. However, the nature of such somatic-derived early embryo has been elusive. Recently, we provided evidence to show that polyploid giant cancer cells (PGCCs), which have been previously considered non-dividing, are actually capable of self-renewal, generating viable daughter cells via amitotic budding, splitting and burst, and capable of acquisition of embryonic-like stemness [ 15 , 16 , 17 ]. The mode of PGCC division is remarkably similar to that of blastomere, a first step in human embryogenesis following fertilization. The blastomere nucleus continuously divides 4–5 times without cytoplasmic division to generate 16–32 cells and then to form compaction/morulae before developing into a blastocyst [ 18 ]. Based on these data and similarity to the earliest stage of human embryogenesis, I propose a new theory that tumor initiation can be achieved via a dualistic origin, similar to the first step of human embryogenesis via the formation of blastomere-like cells, i.e. the activation of blastomere or blastomere-like cells which leads to the dedifferentiation of germ cells or somatic cells, respectively, which is then followed by the differentiation to generate their respective stem cells, and the differentiation arrest at a specific developmental hierarchy leading to tumor initiation [ 19 ]. The somatic-derived blastomere-like cancer stem cell follows its own mode of cell growth and division and is named as the giant cell cycle. This cycle includes four distinct but overlapping phases: the initiation, self-renewal, termination, and stability phases. The giant cell cycle can be tracked in vitro and in vivo due to their salient giant cell morphology (Fig.  1 ).

One mononucleated polyploid giant cancer cell (PGCC) in the background of regular size diploid cancer cells. The PGCC can be seen to be at least 100 times larger than that of regular cancer cells

This new theory challenges the traditional paradigm that cancer is a proliferative disease, and proposes that the initiation of cancer requires blastomere-like division that is similar to that of humans before achieving stable proliferation at specific developmental hierarchy in at least half of all human cancers. This question calls for all investigators in the cancer research community to investigate the role of PGCCs in the initiation, progression, resistance, and metastasis of cancer and to look for novel agents to block the different stages of the giant cell cycle.

The histopathology (phenotype) of cancers has been there all the time. It is just the theory of cancer origin proposed by scientists that changes from time to time. After all, trillions of dollars have been invested in fighting this disease by basing on its genetic origin in the past half-century, yet, little insight has been gained [ 14 ]. Here are two quotes from Einstein: “Insanity: doing the same thing over and over again expecting different results”, and “We cannot solve our problems with the same thinking we used when created them”.

In short, it is time to change our mindset and to start pursuing PGCCs, which we can observe under the microscope. But with very little understanding about these cells, it is time for a shift in paradigm.

Jinsong Liu.

Affiliation

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4095, USA.

Email address

[email protected]

Question 95: How can we accelerate the identification of biomarkers for the early detection of pancreatic ductal adenocarcinoma?

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the world with a dismal 5-year overall survival rate of less than 5%; which has not been significantly improved since the past decades. Although surgical resection is the only option for curative treatment of PDAC, only 15%–20% of patients with PDAC have the chance to undergo curative resection, leaving the rest with only palliative options in hope for increasing their quality of life; since they were already at unresectable and non-curative stages at their first diagnosis.

The lack of specific symptoms in the early-stage of PDAC is responsible for rendering an early diagnosis difficult. Therefore, more sensitive and specific screening methodologies for its early detection is urgently needed to improve its diagnosis, starting early treatments, and ameliorating prognoses. The diagnosis so far relies on imaging modalities such as abdominal ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography (ERCP), and positron emission tomography (PET). One may propose to screen for pancreatic cancer in high-risk populations, which is highly recommended, however screening intervention for all the people is not a wise choice; when considering the relatively low prevalence of PDAC, and the difficulty for diagnosing it in its early stage [ 20 ].

Therefore, alternative diagnostic tools for early detection of PDAC are highly expected. Among the biomarkers currently used in clinical practice, carbohydrate antigen 19–9 (CA19–9) is among the most useful one for supporting the diagnosis of PDAC, but it is neither sufficiently sensitive nor specific for its early detection. Yachida et al. reported in 2010 that the initiating mutation in the pancreas occurs approximately two decades before the PDAC to start growing in distant organs [ 21 ], which indicates a broad time of the window of opportunity for the early detection of PDAC. With the advancement in next-generation sequencing technology, the number of reported studies regarding novel potential molecular biomarkers in bodily fluids including the blood, feces, urine, saliva, and pancreatic juice for early detection of PDAC has been increasing. Such biomarkers may be susceptible to detect mutations at the genetic or epigenetic level, identifying important non-coding RNA (especially microRNA and long non-coding RNA), providing insights regarding the metabolic profiles, estimating the tumor level in liquid biopsies (circulating free DNA, circulating tumor cells and exosomes), and so on.

Another approach to identifying biomarkers for the early detection of pancreatic cancer is using animal models. In spontaneous animal models of pancreatic cancer, such as Kras-mutated mouse models, it is expected that by high throughput analyses of the genetic/epigenetic/proteomic alterations, some novel biomarkers might be able to be identified. For instance, Sharma et al. reported in 2017 that the detection of phosphatidylserine-positive exosomes enabled the diagnosis of early-stage malignancies in LSL-Kras G12D , Cdkn2a lox/lox : p48 Cre and LSL-Kras G12d/+ , LSL-Trp R172H/+ , and P48 Cre mice [ 22 ].

These analyses in clinical samples or animal models hold the clues for the early detection of PDAC, however, further studies are required to validate their diagnostic performance. What’s most important, will be the lining-up of these identified prospective biomarkers, to validate their sensitivities and specificities. This will determine their potential for widespread clinical applicability, and hopefully, accelerate the early diagnosis of PDAC.

Mikiya Takao 1,2 , Hirotaka Matsuo 2 , Junji Yamamoto 1 , and Nariyoshi Shinomiya 2 .

1 Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan; 2 Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

E-mail address

[email protected]; [email protected]; [email protected]; [email protected]

Question 96: Can we improve the treatment outcomes of metastatic pancreatic ductal adenocarcinoma through precision medicine guided by a combination of the genetic and proteomic information of the tumor?

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers, and nearly half of the patients had metastatic PDAC when they are initially diagnosed. When they are accompanied by metastatic tumors, unlike most solid cancer, PDAC cannot be cured with primary surgical resection alone [ 23 , 24 ]. Also, since PDAC has poor responses to conventional therapies, improvements in adjunctive treatment approach including chemo- and immuno-therapy are earnestly required. From this standpoint, recent results regarding the differences in the molecular evolution of pancreatic cancer subtypes provide a new insight into its therapeutic development [ 25 ], which may lead to the improvement of the prognosis of not only metastatic PDAC but also of locally advanced or recurrent PDAC.

In fact, new chemotherapeutic regimens such as the combination of gemcitabine with nab-paclitaxel and FOLFIRINOX have been reported to show improved prognosis despite a lack of examples of past successes in the treatment of patients with metastatic PDAC who had undergone R0 resection [ 26 ]. While many mutations including KRAS , CDKN2A , TP53, and SMAD4 are associated with pancreatic carcinogenesis, no effective molecular targeted drug has been introduced in the clinical setting so far. A recent report of a phase I/II study on refametinib, a MEK inhibitor, indicated that KRAS mutation status might affect the overall response rate, disease control rate, progression-free survival, and overall survival of PDAC in combination with gemcitabine [ 27 ].

While immunotherapy is expected to bring a great improvement in cancer treatment, until now, immune checkpoint inhibitors have achieved limited clinical benefit for patients with PDAC. This might be because PDAC creates a uniquely immunosuppressive tumor microenvironment, where tumor-associated immunosuppressive cells and accompanying desmoplastic stroma prevent the tumor cells from T cell infiltration. Recently reported studies have indicated that immunotherapy might be effective when combined with focal adhesion kinase (FAK) inhibitor [ 28 ] or IL-6 inhibitor [ 29 ], but more studies are required to validate their use in clinical practice.

As such, we believe that if the dynamic monitoring of drug sensitivity/resistance in the individual patients is coupled with precision treatment based on individualized genetics/epigenetics/proteomics alterations in the patients’ tumor, this could improve the treatment outcomes of PDAC.

Mikiya Takao 1,2 , Hirotaka Matsuo 2 , Junji Yamamoto 1 , and Nariyoshi Shinomiya 2.

Question 97: What are the parameters that determine a competent immune system that gives a complete response to cancers after immune induction?

Recently, cancer immunotherapy has shown great clinical benefit in multiple types of cancers [ 30 , 31 , 32 ]. It has provided new approaches for cancer treatment. However, it has been observed that only a fraction of patients respond to immunotherapy.

Much effort has been made to identify markers for immunotherapeutic response. Tumor mutation burden (TMB), mismatch repair (MMR) deficiency, PD-L1 expression, and tumor infiltration lymphocyte (TIL) have been found to be associated with an increased response rate in checkpoint blockade therapies. Unfortunately, a precise prediction is still challenging in this field. Moreover, when to stop the treatment of immunotherapy is an urgent question that remains to be elucidated.

In other words, there is no available approach to determine if a patient has generated a good immune response against the cancer after immunotherapy treatments. All of these indicate the complexity and challenges that reside for implementing novel man-induced cancer-effective immune response therapeutics. A variety of immune cells play collaborative roles at different stages to recognize antigens and eventually to generate an effective anti-cancer immune response. Given the high complexity of the immune system, a rational evaluation approach is needed to cover the whole process. Moreover, we need to perfect vaccine immunization and/or in vitro activation of T cells to augment the function of the immune system; particularly the formation of immune memory.

Edison Liu 1 , Penghui Zhou 2 , Jiang Li 2 .

1 The Jackson Laboratory, Bar Harbor, ME 04609, USA; 2 Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China.

[email protected]; [email protected]; [email protected]

Question 98: Is high local concentration of metformin essential for its anti-cancer activity?

Metformin was approved as a first line of anti-diabetic drug since decades. Interestingly, the fact that clinical epidemiological studies have shown that metformin can reduce the risk of a variety of cancers stimulates considerable recognition to explore its anticancer activity.

Although the in vitro and in vivo experimental results have demonstrated that metformin can have some potential anti-tumor effects, more than 100 clinical trials did not achieve such desirable results [ 33 ]. We and others believe that the main problem resides in the prescribing doses used. For cancer treatment, a much higher dose may be needed for observing any anti-tumor activities, as compared to the doses prescribed for diabetics [ 34 , 35 , 36 ].

Further, if the traditional local/oral administration approach is favored, the prescribed metformin may not be at the required dose-concentration once it reaches the blood to have the effective anti-cancer activities. We, therefore, propose that intravesical instillation of metformin into the bladder lumen could be a promising way to treat for bladder cancer, at least. We have already obtained encouraging results both in vitro and in vivo experiments, including in an orthotopical bladder cancer model [ 36 , 37 ]. Now, we are waiting to observe its prospective clinical outcome.

Mei Peng 1 , Xiaoping Yang 2 .

1 Department of Pharmacy, Xiangya Hospital, Central South University. Changsha, Hunan 410083, P. R. China; 2 Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan 410013, P. R. China.

[email protected]; [email protected]

Question 99: How can we monitor the emergence of cancer cells anywhere in the body through plasma testing?

The early detection of cancer is still a relentless worldwide challenge. The sensitivity and specificity of traditional blood tumor markers and imaging technologies are still to be greatly improved. Hence, novel approaches for the early detection of cancer are urgently needed.

The emergence of liquid biopsy technologies opens a new driveway for solving such issues. According to the definition of the National Cancer Institute of the United States, a liquid biopsy is a test done on a sample of blood to look for tumorigenic cancer cells or pieces of tumor cells’ DNA that are circulating in the blood [ 38 ]. This definition implies two main types of the current liquid biopsy: one that detects circulating tumor cells and the other that detects non-cellular material in the blood, including tumor DNA, RNA, and exosomes.

Circulating tumor cells (CTCs) are referred to as tumor cells that have been shed from the primary tumor location and have found their way to the peripheral blood. CTCs were first described in 1869 by an Australian pathologist, Thomas Ashworth, in a patient with metastatic cancer [ 39 ]. The importance of CTCs in modern cancer research began in the mid-1990s with the demonstration that CTCs exist early in the course of the disease.

It is estimated that there are about 1–10 CTCs per mL in whole blood of patients with metastatic cancer, even fewer in patients with early-stage cancer [ 40 ]. For comparison, 1 mL of blood contains a few million white blood cells and a billion erythrocytes. The identification of CTCs, being in such low frequency, requires some special tumoral markers (e.g., EpCAM and cytokeratins) to capture and isolate them. Unfortunately, the common markers for recognizing the majority of CTCs are not effective enough for clinical application [ 41 ]. Although accumulated evidences have shown that the presence of CTCs is a strong negative prognostic factor in the patients with metastatic breast, lung and colorectal cancers, detecting CTCs might not be an ideal branch to hold on for the hope of early cancer detection [ 42 , 43 , 44 , 45 ].

Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the circulatory system, which is mainly derived from the tumor cell death through necrosis and/or apoptosis [ 46 ]. Given its origin, ctDNA inherently carries cancer-specific genetic and epigenetic aberrations, which can be used as a surrogate source of tumor DNA for cancer diagnosis and prognostic prediction. Ideally, as a noninvasive tumor early screening tool, a liquid biopsy test should be able to detect many types of cancers and provide the information of tumor origin for further specific clinical management. In fact, the somatic mutations of ctDNA in different types of tumor are highly variable, even in the different individuals with the same type of tumor [ 47 ]. Additionally, most tumors do not possess driver mutations, with some notable exceptions, which make the somatic mutations of ctDNA not suitable for early detection of the tumor.

Increased methylation of the promoter regions of tumor suppressor genes is an early event in many types of tumor, suggesting that altered ctDNA methylation patterns could be one of the first detectable neoplastic changes associated with tumorigenesis [ 48 ]. ctDNA methylation profiling provides several advantages over somatic mutation analysis for cancer detection including higher clinical sensitivity and dynamic range, multiple detectable methylation target regions, and multiple altered CpG sites within each targeted genomic region. Further, each methylation marker is present in both cancer tissue and ctDNA, whereas only a fraction of mutations present in cancer tissue could be detected in ctDNA.

In 2017, there were two inspiring studies that revealed the values of using ctDNA methylation analysis for cancer early diagnosis [ 49 , 50 ]. After partitioning the human genome into blocks of tightly coupled CpG methylation sites, namely methylation haplotype blocks (MHBs), Guo and colleagues performed tissue-specific methylation analyses at the MHBs level to accurately determine the tissue origin of the cancer using ctDNA from their enrolled patients [ 49 ]. In another study, Xu and colleagues identified a hepatocellular carcinoma (HCC) enriched methylation marker panel by comparing the HCC tissue and blood leukocytes from normal individuals and showed that methylation profiles of HCC tumor DNA and matched plasma ctDNA were highly correlated. In this study, after quantitative measurement of the methylation level of candidate markers in ctDNA from a large cohort of 1098 HCC patients and 835 normal controls, ten methylation markers were selected to construct a diagnostic prediction model. The proposed model demonstrated a high diagnostic specificity and sensitivity, and was highly correlated with tumor burden, treatment response, and tumor stage [ 50 ].

With the rapid development of highly sensitive detection methods, especially the technologies of massively parallel sequencing or next-generation sequencing (NGS)-based assays and digital PCR (dPCR), we strongly believe that the identification of a broader “pan-cancer” methylation panel applied for ctDNA analyses, probably in combination with detections of somatic mutation and tumor-derived exosomes, would allow more effective screening for common cancers in the near future.

Edison Liu 1 , Hui-Yan Luo 2 .

[email protected]; [email protected]

Question 100: Can phytochemicals be more specific and efficient at targeting P-glycoproteins to overcome multi-drug resistance in cancer cells?

Though several anticancer agents are approved to treat different types of cancers, their full potentials have been limited due to the occurrence of drug resistance. Resistance to anticancer drugs develops by a variety of mechanisms, one of which is increased drug efflux by transporters. The ATP-binding cassette (ABC) family drug efflux transporter P-glycoprotein (P-gp or multi-drug resistance protein 1 [MDRP1]) has been extensively studied and is known to play a major role in the development of multi-drug resistance (MDR) to chemotherapy [ 51 ]. In brief, overexpressed P-gp efflux out a wide variety of anticancer agents (e.g.: vinca alkaloids, doxorubicin, paclitaxel, etc.), leading to a lower concentration of these drugs inside cancer cells, thereby resulting in MDR. Over the past three decades, researchers have developed several synthetic P-gp inhibitors to block the efflux of anticancer drugs and have tested them in clinical trials, in combination with chemotherapeutic drugs. But none were found to be suitable enough in overcoming MDR and to be released for marketing, mainly due to the side effects associated with cross-reactivity towards other ABC transporters (BCRP and MRP-1) and the inhibition of CYP450 drug metabolizing enzymes [ 52 , 53 ].

On the other hand, a number of phytochemicals have been reported to have P-gp inhibitory activity. Moreover, detailed structure–activity studies on these phytochemicals have delineated the functional groups essential for P-gp inhibition [ 53 , 54 ]. Currently, one of the phytochemicals, tetrandrine (CBT-1 ® ; NSC-77037), is being used in a Phase I clinical trial ( http://www.ClinicalTrials.gov ; NCT03002805) in combination with doxorubicin for the treatment of metastatic sarcoma. Before developing phytochemicals or their derivatives as P-gp inhibitors, they need to be investigated thoroughly for their cross-reactivity towards other ABC transporters and CYP450 inhibition, in order to avoid toxicities similar to the older generation P-gp inhibitors that have failed in clinical trials.

Therefore, the selectivity for P-gp over other drug transporters and drug metabolizing enzymes should be considered as important criterias for the development of phytochemicals and their derivatives for overcoming MDR.

Mohane Selvaraj Coumar and Safiulla Basha Syed.

Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.

[email protected]; [email protected]

Question 101: Is cell migration a selectable trait in the natural evolution of carcinoma?

The propensity of solid tumor malignancy to metastasize remains the main cause of cancer-related death, an extraordinary unmet clinical need, and an unanswered question in basic cancer research. While dissemination has been traditionally viewed as a late process in the progression of malignant tumors, amount of evidence indicates that it can occur early in the natural history of cancer, frequently when the primary lesion is still barely detectable.

A prerequisite for cancer dissemination is the acquisition of migratory/invasive properties. However, whether, and if so, how the migratory phenotype is selected for during the natural evolution of cancer and what advantage, if any, it may provide to the growing malignant cells remains an open issue. The answers to these questions are relevant not only for our understating of cancer biology but also for the strategies we adopt in an attempt of curbing this disease. Frequently, indeed, particularly in pharmaceutical settings, targeting migration has been considered much like trying “to shut the stable door after the horse has bolted” and no serious efforts in pursuing this aim has been done.

We argue, instead, that migration might be an intrinsic cancer trait that much like proliferation or increased survival confers to the growing tumor masses with striking selective advantages. The most compelling evidence in support for this contention stems from studies using mathematical modeling of cancer evolution. Surprisingly, these works highlighted the notion that cell migration is an intrinsic, selectable property of malignant cells, so intimately intertwined with more obvious evolutionarily-driven cancer traits to directly impact not only on the potential of malignant cells to disseminate but also on their growth dynamics, and ultimately provide a selective evolutionary advantage. Whether in real life this holds true remains to be assessed, nevertheless, work of this kind defines a framework where the acquisition of migration can be understood in a term of not just as a way to spread, but also to trigger the emergence of malignant clones with favorable genetic or epigenetic traits.

Alternatively, migratory phenotypes might emerge as a response to unfavorable conditions, including the mechanically challenging environment which tumors, and particularly epithelial-derived carcinoma, invariably experience. Becoming motile, however, may not per se being fixed as phenotypic advantageous traits unless it is accompanied or is causing the emergence of specific traits, including drug resistance, self-renewal, and survival. This might be the case, for example, during the process of epithelial-to-mesenchymal transition (EMT), which is emerging as an overarching mechanism for dissemination. EMT, indeed, may transiently equip individual cancer cells not only with migratory/invasive capacity but also with increased resistance to drug treatment, stemness potential at the expanse of fast proliferation.

Thus, within this framework targeting pro-migratory genes, proteins and processes may become a therapeutically valid alternative or a complementary strategy not only to control carcinoma dissemination but also its progression and development.

Giorgio Scita.

IFOM, The FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy; Department of Oncology and Hemato-Oncology (DIPO), School of Medicine, University of Milan, Via Festa del Perdono 7, 20122, Italy.

[email protected]

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Recent Advances and Challenges in Cancer Immunotherapy

Simple summary.

Immunotherapy helps a person’s immune system to target tumor cells. Recent advances in cancer immunotherapy, including immune checkpoint inhibition, chimeric antigen receptor T-cell therapy and cancer vaccination, have changed the landscape of cancer treatment. These approaches have had profound success in certain cancer types but still fail in the majority of cases. This review will cover both successes and current challenges in cancer immunotherapy, as well as recent advances in the field of basic tumor immunology that will allow us to overcome resistance to existing treatments.

Cancer immunotherapy has revolutionized the field of oncology in recent years. Harnessing the immune system to treat cancer has led to a large growth in the number of novel immunotherapeutic strategies, including immune checkpoint inhibition, chimeric antigen receptor T-cell therapy and cancer vaccination. In this review, we will discuss the current landscape of immuno-oncology research, with a focus on elements that influence immunotherapeutic outcomes. We will also highlight recent advances in basic aspects of tumor immunology, in particular, the role of the immunosuppressive cells within the tumor microenvironment in regulating antitumor immunity. Lastly, we will discuss how the understanding of basic tumor immunology can lead to the development of new immunotherapeutic strategies.

1. Introduction

Immunotherapy harnesses a patient’s immune system to target cancer and has resulted in novel therapeutic approaches and unprecedented clinical outcomes [ 1 ]. Although immunotherapeutic approaches have found success in a variety of cancer subtypes and clinical scenarios challenges still remain [ 2 , 3 , 4 , 5 ]. Thus, comprehensive knowledge of how these therapies function is essential to address these challenges [ 6 , 7 ]. Tumor–host immune system interactions are heterogenous and certain characteristics can predict immunotherapy responsiveness. The tumor microenvironment (TME), in particular, affects immunotherapeutic response and immune evasion [ 8 , 9 ]. A deep understanding of host–tumor interactions is critical to fostering the development of novel and more effective immunotherapies. In this review, we will summarize the current landscape of immune checkpoint inhibition (ICI), adoptive cellular therapy (CAR T-cell therapy) and cancer vaccination. We will also outline new standards of care and examine immuno-oncology trials, with a focus on factors that affect immunotherapeutic results. In particular, we will explore the TME and how it influences immunotherapy outcomes and how to potentially address host–tumor interactions to improve immunotherapy efficacy.

2. Current State of Cancer Immunotherapy

2.1. immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors (ICI) are one of the most promising types of cancer immunotherapy. Multiple drugs have received FDA approval for more than nine cancer types over the last decade [ 10 ]. ICI therapy is based on the premise that T cells contain evolutionarily conserved negative regulatory markers that act as “checkpoints” to regulate activation [ 9 ]. Early after activation, T cells upregulate inhibitory receptor cytotoxic T lymphocyte antigen 4 (CTLA4) and, later, programmed cell death 1 (PD-1), which then bind to co-stimulatory ligands B7-1, B7-2 and PD-L1 or PD-L2, respectively [ 11 , 12 ]. Ligands are presented by tumor cells, regulatory T cells (Tregs), myeloid cells and antigen-presenting cells (APCs), which dampen cytotoxic T-cell activation, resulting in immune suppression and tumor growth [ 13 , 14 , 15 ]. Upon treatment with immune checkpoint inhibitors, inhibition is released and cancer cells are targeted and destroyed by the primed and activated cytotoxic T cells [ 16 , 17 ]. ICI has resulted in successful treatment for a variety of recalcitrant cancers [ 18 ].

ICI has achieved marked success in patients with previously dismal outcomes treated with conventional cancer therapies, such as chemo, radiation and targeted therapy. Durable responses suggest long-lasting immunological memory can be seen, established in patients who respond to ICI. FDA-approved ICI therapies are outlined in Table 1 .

FDA approved, combination and ongoing clinical trials with ICI.

Microsatellite instability-high (MSI-H), mismatch repair deficient (dMMR), colorectal cancer (CRC), renal cell carcinoma (RCC), Non-small cell lung cancer (NSCLC), head and neck squamous cell carcinomas (HNSCC), hepatocellular carcinoma (HCC), Classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), Merkel cell carcinoma (MCC), malignant pleural mesothelioma (MPM), triple negative breast cancer (TNBC), solid tumor (ST), myelodysplastic syndrome (MDS), acute myeloid leukemia (AML).

Ipilimumab, a therapeutic anti-CTLA4 human IgG1 monoclonal antibody, was the first ICI approved by the FDA and has since been utilized for treatment in a number of diseases [ 19 , 20 , 21 , 22 , 23 ]. Though some ICIs have been successful, some have also failed. Another anti-CTLA antibody, Tremelimumab, is an IgG2 isotype that failed to meet its primary endpoint in late-stage trials for advanced metastatic melanoma [ 24 , 25 ]. Ipilimumab and tremelimumab appear to have different antibody-dependent cell-mediated cytotoxicity (ADCC) effects, though it is unclear why. These antibodies may mediate depletion of tumor-infiltrating regulatory T cells via ADCC, modulating their clinical outcome [ 26 , 27 ]. Pembrolizumab (pembro) and nivolumab, two human IgG4 anti-PD-1 checkpoint inhibitor antibodies, were the first PD-1-targeted, FDA-approved therapies for refractory and unresectable melanoma [ 23 , 28 , 29 ]. Pembro, in particular, has had marked success, demonstrating an increase in overall response rate (ORR) in NSCLC and in melanoma patients compared to standard-of-care chemo. In certain cases, for melanoma (nivolumab/pembro) and NSCLC (atezolizumab), ICI has become the first line of treatment over chemo [ 30 , 31 , 32 , 33 ]. Combination therapy with anti-CTLA4 + anti-PD-1 has demonstrated significantly improved ORR for metastatic melanoma at 58% [ 34 ]. However, increased toxicity to combined treatment is common and remains a challenge to address.

Increased PD-L1 expression has been found to be associated with improved responses to pembro and PD-L1 expression level is used as a biomarker to guide the indication for ICI in certain cancer subtypes [ 35 , 36 , 37 ]. The type of scoring system used, whether tumor-derived PD-L1, TME-derived PD-L1 or a combined score, is important to note.

Anti-PD-L1 antibody treatments have also been proven effective in multiple types of cancer. Atezolizumab was the first approved anti-PD-L1 ICI for the treatment of urothelial carcinoma, and avelumab and durvalumab are approved for multiple types of solid tumor cancers [ 18 , 23 , 33 , 38 , 39 , 40 , 41 , 42 ]. Tumor PD-L1 expression has also been used as a biomarker for treatment indication for anti-PD-L1 ICI.

Microsatellite instability in cancer results from defective DNA mismatch repair (dMMR) proteins. The presence of microsatellite instability at high levels (MSI-H) has been associated with markedly improved outcomes in multiple cancer subtypes, including ovarian and colorectal cancer (CRC) [ 43 , 44 ]. Dramatically improved outcomes seen with MSI-H and ICI resulted in pembro being the first treatment approved in the disease agnostic setting based on the presence of MSI-H, regardless of cancer subtype [ 45 ]. A recent clinical study with dostarlimab, an anti-PD-1 ICI, in dMMR rectal cancer recently reported 100% clinical ORR and no recurrence to date [ 46 ].

Though ICI results in dramatic results for responders, only 20–30% of patients achieve a clinical response to ICI. Thus, in order to address the majority of patients, a deep understanding of additional checkpoint pathways and how they may be targeted is critical. Table 1 outlines ongoing clinical trials to investigate novel ICI agents. T-cell immunoreceptor with Immunoglobulin (Ig) and ITIM domains (TIGIT) is an inhibitory molecule present on CD8+ and CD4+ T cells, Tregs and natural killer (NK) cells that regulates T-cell immunity via the CD226-PVR pathway. Approximately two dozen monoclonal antibodies targeting TIGIT have been developed as both single agents and to be used in conjunction with anti-PD-1 or anti-PD-L1 agents [ 47 ]. Tiragolumab, an anti-TIGIT IgG1 antibody, when combined with atezolizumab ( Table 1 ) showed improved clinical efficacy in NSCLC vs. atezo plus placebo and is currently being investigated in multiple Phase III trials in solid tumors [ 48 , 49 ]. Other anti-TIGIT antibodies, vibostolimab and etigilimab, have also shown promising clinical activity in early phase studies [ 50 , 51 ]. V-domain Immunoglobulin T-cell activation suppressor (VISTA) is another potential target. VISTA maintains naive T-cell and myeloid cell quiescence through binding to P-selectin glycoprotein ligand-1 (PSGL-1). VISTA binding activity is greater in low-pH and hypoxic settings, such as the TME. VISTA suppresses T-cell activation and reprograms macrophages to an immunosuppressive phenotype in the TME [ 52 , 53 ]. Anti-VISTA antibodies are under development, including a pH-selective VISTA blocking antibody that suppressed tumor growth in a mouse model of colon cancer [ 54 ]. T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is another co-inhibitory molecule expressed on T cells and leukemic cells, such as AML. Multiple Tim-3 inhibitors are being studied and have showed promise in treating MDS and AML ( Table 1 ). Anti-Tim-3 ICI functions to target Tim3-expressing AML cells and boosts antitumor T-cell activity via its ICI activity [ 55 , 56 ].

Although immune checkpoint blockade has achieved remarkable successes, there remain challenges. There is still a significant portion of patients that do not respond at all and adverse effects of ICI, particularly combination therapy, need to be addressed [ 9 , 25 ]. Further study of alternative checkpoint inhibitor pathways that allow tumor escape and the influence of the TME on ICI will also be critical to future success.

2.2. CAR T-Cell Therapy

Adoptive cellular therapy (ACT) traditionally referred to three different approaches: infusion of tumor-infiltrating lymphocytes (TIL), genetically modified T-cell receptor (TCR) therapies and chimeric antigen receptor (CAR)-modified T cells [ 57 ]. The use of other immune cell types, such as natural killer cells (NK), CAR-NK cells, as well as CAR-macrophages (CAR-M), is being studied, though no therapies have yet obtained FDA approval. The most successful ACT has been CAR T-cell therapy (CART), which now carries a multitude of FDA-approved indications and is being utilized as standard of care worldwide for a variety of hematologic malignancies ( Table 2 ). Here, we focus on successes in CART, as well as challenges facing CART and future areas for research.

FDA-approved and ongoing clinical trials with CAR T.

Relapsed/refractory (R/R), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), B-cell non-Hodgkin lymphoma (NHL), Mantle cell lymphoma (MCL), large cell lymphoma (LCL), chronic lymphocytic lymphoma (CLL), small lymphocytic lymphoma (SLL).

CAR T cells were originally described by Eshhar et al., whereby a murine single-chain variable fragment antibody domain (svFC) was linked with a CD3ζ signaling chain and then inserted onto a human T cell. These first-generation CARs allowed for major histocompatibility complex (HLA)-independent activation of T cells when presented with a specific target antigen recognized by the svFC [ 58 ]. In 2011, costimulatory domains (most commonly CD28 or 4-1BB) were added to the CAR construct, resulting in much improved CAR T-cell expansion, persistence and pre-clinical efficacy [ 59 , 60 ]. Ultimately, these “2nd generation” CAR constructs have displayed unprecedented clinical efficacy, particularly when targeted against CD19 expressing B-cell lymphomas and leukemias and against B-cell maturation antigen (BCMA)-expressing multiple myeloma.

CART has found particularly profound success in diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin’s B-cell lymphoma (NHL). In relapsed or refractory (R/R) DLBCL, outcomes were dismal. Patients unfit for or who relapsed after autologous stem cell transplant traditionally had an overall response rate (ORR) to next line of therapy of 20–30%, with a median overall survival (OS) of approximately 6 months [ 61 , 62 , 63 ]. ZUMA-1 (axicabtagene ciloleucel or axi-cel) and JULIET (tisagenlecleucel or tisa-cel) were pivotal trials for an autologous anti-CD19 CART (CAR19) product for patients with R/R DLBCL. Autologous mononuclear cells were collected by apheresis, purified to select for T cells, engineered with an Anti-CD19 scFV, expanded and reinfused into the patient. Both axi-cel (CD28 costimulatory domain) and tisa-cel (4-1BB co-stimulatory domain) had substantial post-infusion expansion in the majority of patients [ 64 , 65 ]. CAR19 provided an unprecedented ORR of 54–82%, a complete response (CR) rate of 40–54% and a median OS measured in years [ 64 , 65 ]. Real-world trials demonstrated comparable results and most patients who achieved a CR and 30–40% of all patients appear to remain in durable remission five years or longer post-CAR infusion [ 66 , 67 , 68 ]. CAR19 is now considered standard of care for R/R aggressive NHL after 2 or more lines of therapy and recent studies support shifting CART to the second line (and for which axi-cel was recently FDA approved) [ 69 , 70 ].

CART has also found success in R/R Multiple Myeloma (MM) by targeting BCMA. Idecabtegene vicleucel was approved in 2021, based on a phase 2 study showing that heavily pre-treated, relapsed refractory patients achieved 73% ORR and 33% CR rate [ 71 ]. Ciltacabtagene autoleucel is a second anti-BCMA CART that did well in heavily pre-treated patients with R/R MM, with a 97% ORR, 67% CR rate and 77% durable response at 1 year [ 72 ]. A retrospective study analyzed a similar cohort of patients who received non-CART therapy and found significantly worse outcomes compared to those seen with CART [ 73 ]. Continued clinical trials will be required to determine the optimal timing or CART in MM.

Four CAR19 agents and two anti-BMCM CART agents have now been FDA approved ( Table 2 ). CART has transformed hematologic cancer treatment, yet challenges remain. The majority of patients who receive CART ultimately fail therapy, whether due to primary progression or response then relapse [ 64 , 65 , 74 ]. In acute lymphoblastic leukemia (ALL), lasting remissions have been demonstrated in pediatrics, but most adult patients require an allogeneic stem cell transplant post CAR19 due to high rates of relapse [ 75 , 76 ]. In order to address these challenges, more research into the mechanisms of CART resistance is required. CART failure includes either primary resistance to CART or response and then relapse post CART; each characteristically results from a different mechanism, though mechanisms of failure may not be mutually exclusive. Causes of CART failure can be grouped into tumor or disease-intrinsic factors, CAR T-cell product-specific mechanisms and CAR T-cell/host interactions. Loss or mutation of the target antigen (e.g., the CD19 extracellular epitope on leukemic/lymphoma cells) results in tumor intrinsic CAR T-cell failure [ 77 , 78 ]. Further, 10–20% of ALL patients will relapse with CD19 (-) leukemia [ 75 , 78 , 79 ]. However, in one study of patients who achieved a CR and then relapsed, 68% relapsed with CD19 (-) disease (with 27% not evaluable and only 4.5% with CD19+ disease). In the pivotal ZUMA-1 trial, 3/11 (27%) patients who failed CART who had evaluable tissue had lost CD19 expression at time of progression [ 64 ]. Alternative antigen and multi-antigen treatments are being developed to address antigen loss. Shah et al. found that anti-CD22-directed CAR T-cell treatment achieved 70% CR rates in ALL after failure of CAR19 [ 80 ]. Clinical trials of anti-CD22 following CAR19 failure in NHL have also been successful [ 81 ]. Though studies are promising, antigen loss of the new target (ex. CD22 or CD20) is also a potential drawback. Thus, several clinical trials integrating multiple antigen targets (ex. CD19/22) on a single CAR are underway, including a tri-specific CART targeting CD19/20/22, soon to open here at the OSUCCC [ 82 , 83 ].

Poor expansion and function are caused by CAR T-cell product intrinsic deficiencies. Clinical performance relies on CART viability, transduction efficiency and phenotype. Inadequate products can be due to manufacturing error, poor culture conditions or low-quality donor T cells due to past therapy and/or high disease burden at the time of apheresis [ 84 ]. Both patient status and the manufacturing process must be optimized to address CART product intrinsic mechanisms of failure [ 80 , 82 ]. Studies evaluating cell product collection pre- and post-bridging therapy and how cytoreduction may affect product quality are required. Point-of-care manufacturing, novel culture conditions and varying culture length are innovative CAR T-cell manufacturing methodologies. Point-of-care manufacturing reduces vein-to-vein time and may improve therapeutic results [ 82 , 85 ]. Recent studies utilizing IL7 and IL15 for the expansion phase of CART culture (instead of IL-2 utilized FDA-approved products) and a shorter 8-day manufacturing period have shown an increase in T stem-cell-like memory populations and have been hypothesized to improve expansion and overall effectiveness [ 86 ]. Commercial production of 4-1BB CAR19 using a 2-day, expansion-free approach has demonstrated encouraging results [ 87 ]. This shorter method boosted stemness and proliferative potential by expanding CAR T cells in vivo (in human), as opposed to ex vivo [ 87 , 88 ].

Tumor, host and CAR T-cell interactions result from interplay of the TME with the infused CAR T-cell product. Immunosuppressive TME interactions with CAR T cells can reduce expansion and increase exhaustion, with host systemic inflammation and tumor burden contributing as well [ 89 , 90 ]. Retrospective studies quantifying risk factors for CAR T-cell failure have identified extranodal disease sites ≥2, increased C-reactive protein and lactate dehydrogenase (inflammatory markers) and high metabolic tumor volume at the time of treatment as predictive of outcomes. [ 91 ] Jain et al. identified increased protumoral tumor-associated macrophage (TAM) markers, increased PD-L1 expression in the TME and increased mononuclear-myeloid-derived suppressor cells (MDSC’s) in circulation as factors that correlated with poorer response to CAR19 [ 92 ]. In CART for solid tumors, a more robust TME and increased tumor heterogeneity are hypothesized to be the primary reason for the lack of efficacy [ 93 ]. Both novel bridging and conditioning regimens, as well as radiation therapy pre-CART, are being studied to abrogate TME-mediated CART inhibition [ 94 , 95 ].

In CLL, Bruton’s Tyrosine Kinase inhibitor (BTKi) use prior to leukapheresis has been shown to improve CAR T-cell expansion and function, decrease T-cell exhaustion and also mitigate toxicity [ 96 , 97 ]. BTKi augments CART function via TME modulation, including reduced PD-1 and CTLA-4 expression, inhibition of Tregs, downregulation of B-cell chemokines and disruption of tumor cell adhesion/homing [ 98 ]. Here, at the Ohio State University Comprehensive Cancer Center (OSUCCC), we have achieved relative success by utilizing ibrutinib through leukapheresis and bridging prior to CAR T-cell therapy in patients with Richter’s Syndrome (DLBCL with antecedent CLL). Five of nine patients treated achieved a CR and four of these remained disease free long term [ 99 ].

Increased PD-L1 expression by TAMs is associated with poorer outcomes in CART [ 92 ]. Zuma-6 investigated the use of anti-PD-L1 atezolizumab post axi-cel infusion. Though atezolizumab was determined to be safe, clinical outcomes were similar to giving axi-cel alone [ 100 ].

Another approach to address mechanisms of CART failure is the use of novel salvage agents. The focus is on restoring CART proliferation and function to recapture a clinical response after failure. In a study of pembro given post-CART failure, 3/12 patients responded to therapy, with only 1 CR. Though outcomes were poor with pembro compared to results seen with other salvage agents, the responders to CAR T cells re-expanded and were more functionally active [ 101 , 102 , 103 ]. Thus, this is proof of concept that CART activity and proliferation can be recaptured post-CART failure with salvate therapy. In a point-of-care manufactured CAR19 product, TIGIT expression post CART was found to be associated with poorer outcomes. Anti-TIGIT ICI rescued CART function in vitro and in vivo and may be a promising agent post-CART failure. Lenalidomide is an immunomodulatory agent that enhances CAR T-cells’ antitumor efficacy by altering tumor cell receptor expression, via modification of the TME landscape and via direct effects on CAR T cells [ 104 , 105 ]. Multiple abstracts and studies have revealed the benefit of lenalidomide containing salvage regimens post CAR T-cell failure and clinical trials to study this further are warranted [ 101 ]. Continued research with robust clinical studies investigating the timing and appropriate population to use post-CAR immunomodulatory agents to enhance CAR T-cell function are required.

CART efficacy has also remained minimal in solid tumors, with no FDA-approved agents as of yet. This is due to both a lack of efficacy and increased toxicity seen in clinical trials [ 106 ]. Solid tumors are highly heterogeneous and CART requires a ubiquitously expressed target on tumor, with relatively low expression on normal tissue [ 106 ]. Further, solid tumors contain a highly robust and immunosuppressive TME, which impairs trafficking to and function within the tumor [ 107 ].

Though CAR T-cell therapy has found unprecedented success in CD19 and BCMA-expressing hematologic malignancies, it has still not been successful in the majority of patients nor in the majority of other hematologic and solid malignancies. In order to address this, further basic research into novel CART cell engineering strategies to enhance tumor recognition, TME infiltration, and improve anti-cancer activity is required.

2.3. Cancer Vaccines

Cancer vaccines aim to generate and amplify pre-existing T-cell and immune responses by providing tumor-specific or tumor-associated antigens (TAA) for elimination by the immune system [ 108 , 109 ]. Cancer vaccines purport to create persistent, targeted anticancer immunity. Developing tumor-specific antigens for cancer vaccines is challenging. TAAs are antigens selectively expressed or overexpressed in malignancies but also expressed in normal tissues. Targeting TAAs may induce autoreactive immune responses, resulting in organ toxicity and autoimmunity. Neoantigens result from carcinogenesis-related gene mutations. Neoantigens, which are not found in normal tissues, can be displayed on target cell surfaces, identified by T cells, and are not influenced by tolerance. Recently, the availability and affordability of next-generation sequencing has led to large-scale identification and the establishment of a plethora of neoantigens as potential immune system targets [ 108 , 109 ]. Cancer vaccine platforms are divided into four categories: cell-based, viral-based, peptide-based and nucleic-acid-based vaccines [ 110 ]. Table 3 outlines both FDA-approved cancer vaccines and ongoing trials. Sipuleucel-T (Provenge) was the first FDA-approved cancer vaccine for metastatic castration-resistant prostate cancer [ 111 ]. It is designed to elicit a prostate-cancer-specific immune response against prostatic acid phosphatase, an overexpressing TAA [ 112 ]. Other cell-based vaccinations include antigen-loaded dendritic cell (DC) vaccines produced from tumor lysates or mRNA, TAA peptides, TAA-coding mRNA or neoantigens. DC vaccines have shown promising results in clinical trials as monotherapy, including resulting in improved OS. Additional adjuvants, such as chemotherapy, could improve vaccine efficacy by inducing the release of danger signals by tumor cells and enhancing the immune response [ 113 , 114 , 115 , 116 ].

FDA approved and examples of ongoing clinical trials for cancer vaccines.

Non-muscle invasive bladder cancer (NMIBC), high grade squamous intraepithelial lesion (HSIL), triple negative breast cancer (TNBC), head and neck squamous cell carcinoma (HNSCC), non-Hodgkin’s lymphoma (NHL), non-small cell lung cancer (NSCLC), Glioma Actively Personalized Vaccine Consortium (GAPVAC), Personalized Neoantigen Cancer Vaccine (PNACV), radiation therapy (RT).

Oncolytic virus immunotherapy attacks tumor cells and stimulates antitumor responses. Herpes simplex virus and the adenovirus are used as vectors for specific genes and tumor antigen expression. Their mass-production speed and extensive host cell tropism have benefited clinical research [ 110 ]. The best clinical progress is T-VEC (Imlygic), a first-generation recombinant herpes simplex virus vector, which is FDA approved for treatment of recurrent unresectable melanoma [ 117 , 118 ]. Additionally, clinical trials with vaccines using adenovirus vectors, carrying immune-stimulating genes or providing TAAs, have induced strong antitumor immunity and been successful in HER2+ breast cancer and BCG-unresponsive non-muscular-invasive bladder cancer [ 119 , 120 ]. Peptide-based vaccines, including chemical and biosynthetic formulations of expected or known tumor antigens, generate a strong immune response against the tumor antigen. Polypeptide vaccine, DSP-788, induces cancer-cell-specific cytotoxic lymphocyte (CTL) and T-helper cell responses in a variety of solid and hematological tumor environments ( Table 3 ) [ 121 ].

Nucleic acid vaccines also generate a robust MHC-I-mediated CD8+ T-cell response [ 110 ]. They can stimulate humoral and cellular immunity and encode full-length tumor antigens, allowing APCs to cross present several epitopes. Several DNA vaccines utilized in the treatment of cervical cancer have shown encouraging clinical efficacy. mRNA vaccines can encode immunostimulants, TAAs and tumor neoantigens. Immunostimulant-encoded mRNAs, such as TriMix, induce tumor cell death and release tumor antigens or are coupled with multiple-TAA-encoded mRNAs that produce robust CD8+ T-cell responses to improve response rates in patients [ 122 ]. mRNA vaccines encoding neoantigens lead to customizable vaccinations. Melanoma patients treated with personalized, multi-peptide NeoVax revealed long-term persistence of neoantigen-specific T cells exhibiting a memory phenotype, multiple TCR clones with distinct functional avidities and evidence of tumor infiltration [ 123 , 124 ]. Similar studies have been recapitulated in glioblastoma patients with comparable antitumor responses [ 125 , 126 ].

For a variety of immunotherapies (ex. ICI), increased tumor mutational burden has been linked to more potent immune responses and improved efficacy of treatments [ 127 , 128 , 129 ]. Neoantigens show strong individual heterogeneity; specific mutations across different types of tumors create different quantities of neoantigens. Thus, it is likely this will drive the application of this therapy to be more personalized [ 109 ]. The complexity of applying a personalized approach to cancer vaccination, with considerations to each individual TME, and further neoantigen study are areas that will benefit from further basic immunologic research in order to inform the development of effective cancer vaccines.

3. Basic Research in Cancer Immunology

3.1. the tumor microenvironment.

Tumor and host interaction shapes local and systemic immunity to promote tumor development and the immunosuppressive tumor microenvironment [ 130 ]. The TME is heterogenous and varies by patient, cancer subtype and stage. TME composition influences cancer immunotherapy patient responses [ 8 ]. To improve immunotherapy efficacy, it is critical to understand TME cellularity and functionally. Tumor cells drive TME formation by forming physical barriers, inhibiting immune cells and recruiting immunosuppressive cells. Tumor cells secrete immunosuppressive cytokines (e.g., TGF-b, IL-10, VEGF), drive expression of inhibitory receptors and ligands (e.g., PD-L1/2, CTLA-4) and reduce tumor-specific MHC-I antigens. Tumor cells can generate chronic, weak antigen signals that drive T-cell reprogramming into an unresponsive, transcriptionally “exhausted” state. They also deplete nutrients and accumulate waste products, such as lactate and kynurenine, which inhibit T cells and create a hostile environment for effector cells [ 5 , 8 ] ( Figure 1 , created with BioRender.com, accessed on 15 August 2022).

Tumor microenvironment.

The TME’s immunosuppressive function depends on the recruitment of stromal cells and immune cells (especially myeloid cells) and their re-direction towards pro-tumoral functions. Tumor stroma, composed of non-immune cells, such as carcinoma-associated fibroblasts (CAFs), tumor-associated vascular endothelial cells (TAECs) and extracellular matrix (ECM) components, forms a physical and immunosuppressive barrier, which allows angiogenesis to occur and spread [ 131 , 132 ]. Tumor cells, myeloid cells and CAFs have a complementary interaction in the TME. CAFs constitute over 80% of cells in pancreatic and breast tumors; these tumors also exhibit increased myeloid cell infiltration [ 132 , 133 , 134 ]. CAFs convert T cells into inducible Tregs and limit T- and NK-cell function. They increase myeloid infiltration, produce tolerogenic dendritic cells (tDCs), activate immunosuppressive M2-phenotypic macrophages by secreting TGF-b/IL-10 and remove APCs by inhibiting signal activity. TAECs influence immune cell movement, tumor cell intravasation and extravasation via angiogenesis [ 131 , 132 ]. TAECs can serve as non-professional APCs because they lack CD80 and CD86 co-stimulatory expression, triggering antigen-experienced T-cell effector capabilities but not naïve T cells. As non-professional APCs, TAECs reduce antitumor immunity and promote tumor growth [ 132 ].

Tumor-infiltrating lymphocytes (TILs) are various subsets of lymphocytes that are recruited into the TME. Their function depends greatly on TME composition and interacting pathways. TILs include CD8+ CTLs, CD4+ T-helper cells, Tregs, innate lymphoid cells (ILCs), NK cells and natural killer T (NKT) cells. CD8:CD4 TIL ratios have been studied as biomarkers in metastatic melanoma, NSCLC and colon cancer, with certain ratios correlating with increased ICI response predictions, diagnosis and survival rates in patients [ 1 , 8 , 135 , 136 ]. Immunologically “hot” tumors have heavy TIL infiltration. “Cold” tumors lack TILs and are unable to recruit/activate immune cells [ 137 ]. Hot tumors with inflammatory gene signatures respond better to ICI, while cold tumors are resistant [ 138 ]. These inflammatory gene signatures could be used as a clinical prognostic tool to evaluate ongoing trials and to help explain hot vs. cold TME status [ 137 ]. Tumor cells may induce cold TME by exhausting or functionally suppressing lymphocytes that enter the TME. Anti-angiogenic treatment combined with ICI to create high endothelial venules (HEVs) in the TME may enhance activated T-cell infiltration [ 139 ]. This was demonstrated in breast, pancreatic and glioblastoma tumor models, which are cold tumors, leading to sensitization of the TME for ICI and CART therapies [ 139 , 140 ]. Other autophagy-inhibiting targets may inhibit tumor growth in melanoma and CRC while enhancing ICI efficacy [ 141 ]. Continued research on novel methods to transform immune-cold environments into immune-hot environments is ongoing.

T-cell exhaustion is an area that has been extensively researched. Exhausted T cells can be “pre-exhausted” or “terminally exhausted” with increasing expression of immune checkpoints, such as CTLA-4, PD-1, Tim-3, lymphocyte activation gene-3 (LAG-3) and TIGIT, denoting a more terminally exhausted state [ 8 ]. Poor self-renewal, disrupted metabolism and gradual effector function loss characterize these cells [ 5 , 131 ]. In preclinical melanoma, ovarian, breast and bladder cancer models, targeting PI3K/Akt or Wnt, which control CD8+ T-cell infiltration and cytotoxicity and selectively inhibit Treg proliferation, enhances antitumor immunity and promotes tumor regression. Combinational therapies to normalize or sensitize the TME may improve ICI treatment efficacy [ 142 , 143 , 144 , 145 , 146 , 147 , 148 ].

3.2. Tumor-Associated Macrophages and Other Immunosuppressive Myeloid Cells

TAMs constitute most of the non-tumor stromal mass in solid tumors and modulate tumor growth and immunosuppression within the TME [ 149 ]. TAMs are protumoral and have M2-like functions [ 150 , 151 ]. They promote tumor growth and metastasis via anti-inflammatory cytokine secretion and immunosuppressive immune cell interactions and recruitment [ 152 , 153 , 154 ]. Similar to TAMs, myeloid-derived suppressor cells (MDSCs) are pathologically activated, immature, potent immunosuppressive cells at various stages in differentiation [ 155 , 156 ]. They are subdivided into mononuclear MDSCs (M-MDSCs), morphologically similar to blood monocytes, and polymorphonuclear (PMN-MDSCs), which are morphologically similar to neutrophils [ 157 ]. Their recruitment from bone marrow to secondary lymphoid organs and TME by cancer-cell-secreted growth factors promotes overall protumorgenic activity by inducing NK and T-cell inhibition, allowing tumor immunoevasion [ 158 ]. Poor prognosis and OS were correlated with solid tumor MDSC abundance [ 159 , 160 ]. Tumor-associated neutrophils (TANs) also have critical functions within the TME. N1s instruct effector T cells to reject tumor cells and N2s dampen the immune system by enlisting M2s and Tregs [ 132 ]. Shorter survival rates in HCC and poor prognosis for DLBCL have both been associated with TANs [ 161 , 162 ]. Due to their abundance in blood and their immediate reaction to inflammation and injury, their influence in the TME can set the tone for other immunosuppressive cells. DCs also infiltrate the TME but quickly adapt regulatory or tolerogenic phenotypes that promote tumor growth and immunoevasion [ 163 , 164 , 165 ]. Conventional DC types 1 (cDC1) and 2 (cDC2) play a key role as APCs and activate T cells for antitumor responses [ 166 , 167 , 168 ]. cDC1s and cDC2s in the TME are associated with a good prognosis in various cancers, while plasmacytoid DCs (pDC) frequencies are associated with a worse PFS and OS [ 169 , 170 , 171 , 172 , 173 ].

TAM functions are influenced by the TME, cancer type and stage [ 174 ]. Petty et al. described the role of hedgehog (Hh) signaling in polarizing TAMs towards an M2 phenotype and regulating CD8+ T-cell-mediated antitumor immunity [ 175 , 176 ]. Tumor-derived sonic hedgehog (SHH), a Hh ligand, drives TAM M2 polarization resulting in downregulation of CXCL9 and CXCL10 signaling and suppression of CD8+ infiltration into the TME [ 175 ]. TAMs also inhibit CD8+ T-cell activation by depleting essential metabolites for proliferation [ 174 ]. They inhibit T-cell function by producing IL-10, TGF-b and PGE-2 and upregulating PD-L1 [ 174 , 176 , 177 ]. TAMs are a major source of elevated CCL2 expression in human glioblastoma, which correlates with reduced OS, through promotion of CCR2+ M-MDSC infiltration [ 178 , 179 ].

TAMs correlate with poor outcomes in many cancer subtypes [ 180 ]. TAMs’ role as major carriers of checkpoint inhibitor ligands (e.g., PDL-1/2, B7-H4, VISTA) and as mediators of T-cell exhaustion has been well described [ 181 ]. Studies have also revealed how an increased concentration of M2-polarized TAMs mediate anti-PD-L1 ICI resistance in HNSCC and in prostate cancer [ 182 , 183 ].

Given their role in modulating immunotherapy, TAMs represent a promising target to augment immunotherapy. Reducing TAM presence in the TME by depletion or preventing trafficking and reprogramming TAMs to an immune-activating, M1-like phenotype are approaches being studied. Trabectedin is an FDA-approved agent for soft tissue sarcoma which targets TAMs to inhibit CCL2 and IL-6 production. When used in combination with an anti-PD-1 ICI in an ICI-resistant pre-clinical sarcoma model, trabectedin allowed for the recapture of response to anti-PD-1 therapy [ 184 ]. Targeting of PI3k-γ in myeloid cells using eganelisib (IPI-549) has also shown promise in pre-clinical models by restoring sensitivity to ICI [ 185 , 186 ].

Studies evaluating the repolarization of TAMs to a more M1-like, T-cell-activating phenotype are ongoing. Activation of toll-like receptors (TLR) on macrophages can lead to M1 polarization. Local delivery of a TLR7/8 agonist, telratolimod, in combination with ICI in murine melanoma boosted both local and systemic antitumor immunity [ 187 ]. Another novel approach utilizes low-pathogenicity influenza aviruses (IAVs), which have both oncolytic activity and also result in significant repolarization of TAMs to an M1-like state. When IAVs were combined with a novel B7-H3 ICI, responses were dramatic in a resistant NSCLC model [ 188 ]. Hh signaling blockade with vismogedib reduced TAM M2 polarization, increased CD8+ T-cell infiltration and suppressed tumor growth in murine lung and HCC [ 175 ]. Synergy between Hh inhibition and ICI was demonstrated as well with greater reduction in tumorigenesis than seen in either agent alone [ 175 ]. CART (and, in particular, CART targeting solid tumors with a more robust TME) and ICI may benefit from innovative approaches to abrogate TAMs’ immunosuppressive activity in the TME.

3.3. Approaches to Enhance ICI Therapy

Given the response rates seen thus far with currently FDA-approved ICI therapies, it is unlikely that one type of ICI will overcome the various mechanisms of resistance employed by different types of tumors. Targeting aspects of the TME to overcome tumor resistance has shown promise in enhancing ICI therapy [ 189 ].

Targeting the CXCR4/CXCL12 (SDF-1) signaling pathway can help overcome the physical barrier of the TME and enhance ICI. CXCR4 is upregulated on MDSC/TAMs, playing a role in intratumoral fibrosis, and is associated with poor prognosis in several types of cancer. Nanocomplex technology, polymer-based combinatory approaches and liposomal formation have been used to combine anti-PD-L1 agents and CXCR4 antagonists to overcome ICI resistance [ 190 , 191 , 192 ]. Increased effector T-cell infiltration, decreased Treg and MDSC populations and inhibition of primary tumor growth and metastasis were all observed in several tumor models. Nanoparticle technology applying a CSF1R inhibitor in combination with ICI allowed for the development of a sustained codelivery method that successfully reprogramed TAMs to an antitumoral M1-like phenotype and enhanced their phagocytic capabilities in a melanoma model [ 193 ]. In glioblastoma, overcoming the TME physical barrier is also being explored. One group combined brain-tumor-targeted peptide-coated extracellular vesicles, loaded with small interfering RNA (siRNA) against PD-L1, and then delivered them with bursts of radiation therapy [ 194 ]. Dual inhibition of PI3K/mTOR pathway combined with the microtubule targeting chemotherapy, paclitaxel, along with ICI, induced sustainable DC, T cell and NK responses, both locally in the TME and systemically [ 195 ]. Similar results targeting cancer stem cells with the polyketide antibiotic, Mithraymcin-A, and ICI in a CRC mouse model resulted in turning an immunologically cold tumor hot by increasing CD8+ T-cell infiltration and decreasing quantities of MDSC/TAMs in the TME [ 196 ].

New ICI targets are currently being studied as well. NKG2A is a checkpoint inhibitor expressed on subsets of cytotoxic T cells and NK cells. It binds to the MHC-I molecule HLA-E (Qa-1b mouse homolog) and is regulated in a TAP1-dependent manner [ 197 ]. Co-deletion of TAP-1/Qa-1b or blocking NKG2A with monalizumab unleashed effector cell activity and reversed resistance to ICI, resulting in tumor control [ 198 , 199 ]. Another target previously mentioned, used as both a monotherapy and in combination with ICI, is VISTA. Preclinical studies using L557-0155, an inhibitor for VSIG-8 (a VISTA receptor) promoted cytokine production by T cells and suppressed melanoma growth [ 200 ]. An orally administered combinatory small molecular inhibitor of VISTA and PD-L1, CA-170, showed similar antitumor efficacy in a number of mouse tumor models, prompting advancement towards clinical trials [ 201 ].

Diverse techniques to overcome mechanisms of resistance to ICI, including the immunosuppressive TME, as well as alternative ICI pathways that allow for tumor escape are ongoing. Continued focus on turning these basic discoveries into clinically applicable therapies to augment ICI is required.

3.4. Strategies to Improve CART Therapy

CART efficacy has achieved a high degree of success in hematologic malignancies. However, certain patients with risk factors, such as tumor bulk and a highly immunosuppressive TME, have worse outcomes. CART in solid tumors, in particular, has been characterized by a lack of efficacy due to the highly immunosuppressive TME present, resulting in impaired CART trafficking and suppressed proliferation and activation within tumors [ 107 ].

The TME inhibits trafficking and CART by producing suppressive soluble factors and overexpressing negative immune checkpoints. Strategies to deplete immunosuppressive elements of the TME, such as TAMs, to negate these effects are being studies. TAMs and PD-L1 expression reduce CART expansion and result in increased exhaustion, according to multiple studies [ 90 , 92 ]. PF-04136309, a small-molecule inhibitor of the CCL2-CCR2 axis responsible for TAM recruitment, has been used in pancreatic adenocarcinoma with chemo to reduce TAM and Treg infiltration and increase CD4+ and CD8+ effector cell presence in the tumor stroma [ 202 ]. This agent has been proposed for use as part of novel conditioning regimens prior to CART to help reduce TAM-mediated suppression of CART expansion and function [ 202 ]. Blockage of colony-stimulating factor 1 receptor (CSF1R) signaling, involved in TAM recruitment, with pexidartinib (PLX3397), improved the efficacy of adoptive cell transfer in murine melanoma through inhibition of TAM recruitment and activation [ 203 ]. Folate receptor beta (FR) is highly expressed in M2-polarized protumoral TAMs. Anti-FR targeting CAR T-cells was utilized to condition melanoma and colon cancer prior to antigen-specific CART therapy and improved outcomes in CART-resistant murine models [ 204 ].

New CAR T-cell engineering strategies have also been used to boost tumor infiltration and anti-cancer activity in the hostile TME [ 205 , 206 ]. A CCL19/IL7 secreting anti-mesothelin CART product was used increase CART and non-CAR T-cell infiltration into the TME, resulting in growth inhibition of xenografted pancreatic cancer. An IL-15/IL-21 secreting CAR targeting GPC3 in HCC was used and found to help maintain TCF1 expression (critical for T-cell development, proliferation and memory formation in CART). This resulted in robust proliferation and expansion as well as superior tumor control and survival in mice [ 207 ]. One promising method is the use of TGF-beta knockouts to engineer CARTs more resistant to immunosuppression. A TGF-beta 2 receptor knockout CART, developed using the CRISPR/Cas9 system, was found to reduce Treg-induced conversion, prevent CART exhaustion, improve in vivo elimination of tumor and improve CART memory subset formation to improve long-term efficacy [ 208 ]. One novel CART product was engineered to express CCR8 to improve homing to the site of the tumor, as well as a dominant negative TGF-beta 2 receptor to shield CART from TME-derived immunosuppression. This resulted in increased and more sustained infiltration of CARTs in xenografted cancer models [ 209 ]. Continued work developing these novel engineered CARTs into clinical-grade products is required to determine what strategies may provide the best outcomes and provide more insight into what is efficacious in solid tumors.

3.5. Neoantigens in Cancer Vaccination

Neoantigen vaccinations elicit a more powerful and specialized immune response than self-derived TAA vaccines [ 108 ]. Next-generation sequencing (NGS) of tumor DNA has led to customized clinical recombinant vaccines [ 210 , 211 ]. A patient’s HLA alleles might be used to identify a TAA or neoantigen for vaccine development and Sahin et al. demonstrated NGS-derived neoantigens elicit strong CD4+ and CD8+ responses [ 127 , 212 , 213 ]. New study domains include choosing and predicting how a vaccination strategy would function and utilizing aspects of the TME to assist these efforts.

Although early neoantigen vaccine trials have shown promising results, there remain failures and eliciting stronger antitumor responses is a continued goal. Coupling the binding properties of MHC-I with MHC-II has also presented challenges. A single MHC-I neoantigen is insufficient for antitumor immunity in murine models; thus, individualized vaccines should comprise neoepitopes expected to bind to MHC-I and MHC-II alleles [ 214 , 215 ]. MHC-II molecules have increased diversity and their open binding pockets make it difficult to predict a suitable binding motif [ 216 ]. Deep learning approaches that utilize artificial neural networks, inspired by biological neural networks, to predict ligand binding epitopes of MHC molecules are currently being investigated [ 217 , 218 , 219 , 220 ]. MARIA, a deep learning model, was used to analyze T-cell response data from a melanoma neoantigen vaccine study. This study demonstrated neoantigen candidates with high projected MARIA scores produced a CD4+ T-cell response post vaccination [ 221 ]. New AI-based applications and increased processing power help curb the complexity in predicting clinical outcomes and can begin closing knowledge gaps [ 215 ].

Although vaccines used as monotherapy show some potency, it is hypothesized that the vaccine-activated T cells are still suppressed by the TME. Combination approaches have been investigated clinically with current vaccines and also led to new insights in preclinical studies. Vaccines can reshape the TME, improving their effectiveness. Both combination and monotherapies used to enhance specific immune facets within the TME have shown potential to enable cytotoxic effects of vaccines in preclinical studies. Strategies, such as directly targeting TME vasculature (angiogenesis), targeting CAFs, and persistent cytokines, such as GM-CSF, IDO1, BAFF and other interleukins, with cancer vaccines have shown relatively consistent antitumoral effectiveness in preclinical models [ 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 ]. DNA vaccines utilizing novel nanobiomaterials include minimally invasive, injectable smart hydrogels [ 230 ]. These are scaffold-based cancer vaccines that allow for spatial and temporal control of antigen and other therapeutic agents and have shown strong antitumor effects via increased DC infiltration [ 231 ]. Targeting TAM infiltration, activity and polarization is also essential in the delivery of cancer vaccines. Combinatorial techniques have utilized biomimetic recombinant bacterial and viral vectors, nanoparticle and nanoemulsion technology for M1 agonists [ 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 ]. These have shown remarkable therapeutic efficacy through recruitment of lymphocytes, phenotypic transformation of macrophages from M2 to M1 and restoration of exhausted T lymphocytes, enhancing their ability to kill cancer cells in tumor models. With a deeper knowledge of bidirectional communication within the TME, future research will examine cancer vaccines that target immune pathways in the TME to boost vaccination efficacy. Neoantigen identification has developed greatly in the past decade, attributable to NGS, increasing computer capacity and better algorithms. Clinical studies that examine neoantigens as single or combinatorial immunotherapy targets are required to enhance this promising technology.

4. Conclusions and Future Directions

Over the last decade, cancer immunotherapy has markedly changed how we treat cancer patients. Immunotherapeutic modalities have found great success in a wide variety of settings and in patients with previously refractory disease. However, challenges remain. Further study of alternative checkpoint inhibitor pathways that allow for tumor escape and understanding the TME’s suppressive effect on ICI are critical areas of study required to develop more successful ICI therapies. CART has found good success in subsets of patients with hematologic malignancies but not for patients with a highly immunosuppressive TME nor with solid tumors. Targeting the immunosuppressive elements of the TME, including TAMs, has shown promise in improving both ICI and CART efficacy. Clinical studies utilizing these agents, either as pre-conditioning or in combination with ICI and CART, will be required to determine which approaches show the most promise. Targeting elements of alternative pathways with ICI has shown promise and will likely pave the way for new combination therapies. Novel engineering of CART to allow for improved CART trafficking and reduced immunosuppression within solid tumors may finally allow for improved outcomes to be obtained. Cancer vaccines have made great strides as well in recent years. In particular, studies utilizing neoantigen vaccines in combination with TME targeting have the potential to open up this exciting field.

Cancer immunotherapy is a modality that is rapidly becoming critical to the treatment of the majority of cancers. A continued focus on basic immuno-oncology research will drive our ability to develop novel therapies in the field and continue to drive successes on top of those we have achieved with cancer immunotherapy to date.

Funding Statement

This work was supported by NIH grants CA193167, HL151195 and CA260858.

Author Contributions

Conceptualization: C.P., N.D. and Y.Y.; Writing—original draft: C.P. and N.D.; Writing—review and editing: C.P., N.D. and Y.Y.; Visualization: C.P.; Supervision: N.D. and Y.Y. All authors have read and agreed to the published version of the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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New cancer treatment may reawaken the immune system

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Immunotherapy is a promising strategy to treat cancer by stimulating the body’s own immune system to destroy tumor cells, but it only works for a handful of cancers. MIT researchers have now discovered a new way to jump-start the immune system to attack tumors, which they hope could allow immunotherapy to be used against more types of cancer.

Their novel approach involves removing tumor cells from the body, treating them with chemotherapy drugs, and then placing them back in the tumor. When delivered along with drugs that activate T cells, these injured cancer cells appear to act as a distress signal that spurs the T cells into action.

“When you create cells that have DNA damage but are not killed, under certain conditions those live, injured cells can send a signal that awakens the immune system,” says Michael Yaffe, who is a David H. Koch Professor of Science, the director of the MIT Center for Precision Cancer Medicine, and a member of MIT’s Koch Institute for Integrative Cancer Research.

In mouse studies, the researchers found that this treatment could completely eliminate tumors in nearly half of the mice.

Yaffe and Darrell Irvine, who is the Underwood-Prescott Professor with appointments in MIT’s departments of Biological Engineering and Materials Science and Engineering, and an associate director of the Koch Institute, are the senior authors of the study, which appears today in Science Signaling . MIT postdoc Ganapathy Sriram and Lauren Milling PhD ’21 are the lead authors of the paper.

T cell activation

One class of drugs currently used for cancer immunotherapy is checkpoint blockade inhibitors, which take the brakes off of T cells that have become “exhausted” and unable to attack tumors. These drugs have shown success in treating a few types of cancer but do not work against many others.

Yaffe and his colleagues set out to try to improve the performance of these drugs by combining them with cytotoxic chemotherapy drugs, in hopes that the chemotherapy could help stimulate the immune system to kill tumor cells. This approach is based on a phenomenon known as immunogenic cell death, in which dead or dying tumor cells send signals that attract the immune system’s attention.

Several clinical trials combining chemotherapy and immunotherapy drugs are underway, but little is known so far about the best way to combine these two types of treatment.

The MIT team began by treating cancer cells with several different chemotherapy drugs, at different doses. Twenty-four hours after the treatment, the researchers added dendritic cells to each dish, followed 24 hours later by T cells. Then, they measured how well the T cells were able to kill the cancer cells. To their surprise, they found that most of the chemotherapy drugs didn’t help very much. And those that did help appeared to work best at low doses that didn’t kill many cells.

The researchers later realized why this was so: It wasn’t dead tumor cells that were stimulating the immune system; instead, the critical factor was cells that were injured by chemotherapy but still alive.

“This describes a new concept of immunogenic cell injury rather than immunogenic cell death for cancer treatment,” Yaffe says. “We showed that if you treated tumor cells in a dish, when you injected them back directly into the tumor and gave checkpoint blockade inhibitors, the live, injured cells were the ones that reawaken the immune system.”

The drugs that appear to work best with this approach are drugs that cause DNA damage. The researchers found that when DNA damage occurs in tumor cells, it activates cellular pathways that respond to stress. These pathways send out distress signals that provoke T cells to leap into action and destroy not only those injured cells but any tumor cells nearby.

“Our findings fit perfectly with the concept that ‘danger signals’ within cells can talk to the immune system, a theory pioneered by Polly Matzinger at NIH in the 1990s, though still not universally accepted,” Yaffe says.  

Tumor elimination

In studies of mice with melanoma and breast tumors, the researchers showed that this treatment eliminated tumors completely in 40 percent of the mice. Furthermore, when the researchers injected cancer cells into these same mice several months later, their T cells recognized them and destroyed them before they could form new tumors.

The researchers also tried injecting DNA-damaging drugs directly into the tumors, instead of treating cells outside the body, but they found this was not effective because the chemotherapy drugs also harmed T cells and other immune cells near the tumor. Also, injecting the injured cells without checkpoint blockade inhibitors had little effect.

“You have to present something that can act as an immunostimulant, but then you also have to release the preexisting block on the immune cells,” Yaffe says.

Yaffe hopes to test this approach in patients whose tumors have not responded to immunotherapy, but more study is needed first to determine which drugs, and at which doses, would be most beneficial for different types of tumors. The researchers are also further investigating the details of exactly how the injured tumor cells stimulate such a strong T cell response.

The research was funded, in part, by the National Institutes of Health, the Mazumdar-Shaw International Oncology Fellowship, the MIT Center for Precision Cancer Medicine, and the Charles and Marjorie Holloway Foundation.

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104 Cancer Essay Topic Ideas & Examples

Inside This Article

Cancer is a complex and devastating disease that affects millions of people worldwide. Writing an essay on this topic allows for a deeper understanding of the various aspects of cancer, including its causes, prevention, treatment, and impact on individuals and society. Here are 104 cancer essay topic ideas and examples to guide and inspire your writing:

• The history of cancer research and treatment: From ancient times to modern advancements.
• The role of genetics in cancer development: Exploring inherited and acquired genetic mutations.
• Environmental factors and their association with cancer risk: Analyzing the impact of pollution, radiation, and lifestyle choices.
• The most common types of cancer: In-depth exploration of breast, lung, prostate, colorectal, and other prevalent cancers.
• Childhood cancer: Understanding the unique challenges and treatment options for pediatric patients.
• The emotional and psychological impact of cancer on patients and their families.
• The economics of cancer: Assessing the financial burden on patients and healthcare systems.
• The impact of cancer on caregiver mental health: Examining the emotional toll on those who support cancer patients.
• The role of exercise and nutrition in cancer prevention and recovery.
• The development and effectiveness of cancer vaccines: Discussing breakthroughs and future prospects.
• The influence of lifestyle choices on cancer risk: Tobacco, alcohol, diet, and exercise.
• The stigma surrounding cancer: Addressing societal attitudes and misconceptions.
• Alternative therapies for cancer treatment: Exploring complementary medicine and its potential benefits.
• The ethics of experimental cancer treatments: Balancing patient rights and scientific progress.
• Cancer prevention strategies in low-income countries: Identifying challenges and potential solutions.
• The impact of cancer on workplace productivity: Analyzing the economic consequences for employees and employers.
• Cancer survivors' quality of life: Examining the long-term physical and emotional effects.
• The role of support groups and counseling in cancer care: Assessing their benefits and limitations.
• Cancer and gender: Investigating the disparities in cancer incidence, treatment, and outcomes.
• The psychological impact of cancer on children and adolescents.
• The role of technology in early cancer detection: Discussing advancements in screening methods.
• The impact of cancer on sexual health and intimacy: Addressing the challenges and available support.
• The correlation between cancer and mental health disorders: Analyzing the reciprocal relationship.
• The impact of cancer on fertility and reproductive choices: Exploring the options available to patients.
• The intersection of cancer and chronic diseases: Investigating the complexities of dual diagnoses.
• The role of palliative care in cancer treatment: Discussing end-of-life care and patient comfort.
• The influence of social media on cancer awareness and fundraising campaigns.
• The role of governmental policies in cancer prevention and control.
• Cancer and the elderly population: Addressing unique challenges and treatment approaches.
• The impact of race and ethnicity on cancer disparities: Investigating socioeconomic and cultural factors.
• The effects of cancer on children's education and academic development.
• The role of artificial intelligence in cancer diagnosis and treatment planning.
• Cancer prevention campaigns: Analyzing their effectiveness and potential limitations.
• The impact of cancer on sexual minorities: Investigating disparities in diagnosis, treatment, and support.
• The role of spirituality and faith in cancer patients' coping mechanisms.
• Cancer prevention in the workplace: Assessing occupational hazards and protective measures.
• The correlation between cancer and obesity: Exploring the link and potential interventions.
• The impact of cancer on siblings: Addressing the emotional and practical challenges.
• The role of precision medicine in personalized cancer treatment: Discussing targeted therapies.
• The influence of media portrayal on public perception of cancer and cancer patients.
• The impact of cancer on caregivers' professional lives: Analyzing the challenges and potential support systems.
• Cancer and the LGBTQ+ community: Investigating unique challenges and disparities in healthcare access.
• The role of music and art therapy in cancer care: Assessing their benefits and limitations.
• The correlation between cancer and socioeconomic status: Analyzing the disparities in diagnosis and outcomes.
• The impact of cancer on young adults: Discussing fertility preservation and long-term survivorship issues.
• Cancer and the rural population: Addressing barriers to access and treatment options.
• The role of emotional support animals in cancer care: Investigating their benefits and ethical considerations.
• The impact of cancer on intimate partner relationships: Addressing the challenges and available resources.
• The influence of mindfulness and meditation on cancer patients' well-being.
• The impact of cancer on military veterans: Analyzing the intersection of post-traumatic stress disorder and cancer.
• Cancer and the incarcerated population: Addressing the challenges and potential solutions.
• The role of patient advocacy in cancer care: Discussing the importance of empowering patients.
• Cancer prevention through public health initiatives: Assessing community-based interventions.
• The correlation between cancer and air pollution: Investigating the link and potential policy implications.
• The impact of cancer on body image and self-esteem: Addressing psychological and social consequences.
• Cancer and the transgender population: Exploring unique challenges and healthcare disparities.
• The role of social determinants of health in cancer outcomes: Analyzing the influence of socioeconomic factors.
• Cancer and the homeless population: Addressing the barriers to access and supportive care.
• The impact of cancer on the LGBTQ+ youth: Investigating mental health disparities and support systems.
• Cancer prevention in minority populations: Analyzing cultural factors and tailored interventions.
• The role of exercise in cancer rehabilitation: Discussing the benefits of physical activity during and after treatment.
• Cancer and the refugee population: Addressing the challenges and barriers to healthcare.
• The impact of cancer on veterans' mental health: Analyzing post-traumatic stress disorder and survivorship.
• The correlation between cancer and sleep disturbances: Investigating the link and potential interventions.
• Cancer and the disabled population: Addressing unique challenges and supportive care.
• The role of artificial intelligence in cancer prognosis: Discussing predictive models and decision support systems.
• Cancer prevention through HPV vaccination: Analyzing the impact on cervical and other related cancers.
• The impact of cancer on children's social development and peer relationships.
• Cancer and the prison population: Addressing the disparities in access and treatment.
• The role of telemedicine in cancer care: Discussing remote consultations and monitoring.
• Cancer prevention in the aging population: Analyzing challenges and tailored interventions.
• The correlation between cancer and smoking: Investigating the link and effective cessation strategies.
• Cancer and mental health: Exploring the reciprocal relationship and potential interventions.
• The impact of cancer on the LGBTQ+ elderly population: Addressing unique challenges and supportive care.
• Cancer prevention through lifestyle modifications: Analyzing the role of diet, exercise, and stress management.
• The role of genetic counseling in cancer risk assessment: Discussing the benefits and ethical considerations.
• Cancer and environmental justice: Analyzing disparities in exposure to carcinogens.
• The impact of cancer on adolescents' educational attainment and career prospects.
• Cancer and the indigenous population: Addressing cultural and access barriers to care.
• The role of social media influencers in cancer awareness campaigns: Assessing their impact and ethical considerations.
• Cancer prevention through workplace policies: Analyzing the importance of occupational safety measures.

These essay topic ideas offer a wide range of possibilities for exploring the complex and multifaceted nature of cancer. Depending on your interests and expertise, you can choose a topic that resonates with you and delve into it with extensive research, analysis, and critical thinking. Remember to approach the topic with sensitivity and empathy, as cancer affects millions of lives and demands a compassionate approach to understanding and addressing its challenges.

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271 Cancer Research Topics for Undergraduates and High School Students

Are you looking for the best oncology research topics? You’re at the right place! StudyCorgi has prepared a list of cancer research topics for undergraduates and high school students! Read on to find a good title for your projects or term papers on prostate, breast, and other cancer types.

🏆 Best Research Topics on Cancer

✍️ cancer essay topics for college, 👍 good cancer research topics & essay examples, 📝 current cancer titles for essays, 🎓 interesting cancer topics to write about, 💡 simple cancer research paper topics, 📌 easy cancer essay topics, ❓ questions about cancer research, 🗣️ cancer topics for presentation, 🏥 cancer project ideas.

• The Cobalt-60 Machine in the Fight Against Cancer
• The New Cancer Cure
• Breast Cancer: The Story of One Patient
• The Colon Cancer: Main Aspects
• Cultural Sensitivity in Medicine and Cancer Treatment
• Cancer: Symptoms and Consequences
• Lung Cancer Pathophysiology
• Breast Cancer: Literature Review Breast cancer is the single most common type of cancer among women. This type of cancer can be detected by such simple methods as (BSE) breast self-examination.
• Type C Personality as a Risk Factor for Cancer The paper is on the scientific relationship between personality C and the aspects of gene and hormonal activity that leads to the build-up of cancer cells.
• Disease Research: Breast Cancer Breast cancer is a multifactorial, complex illness that demands proper clinical understanding and a multidisciplinary way to determine diagnosis and treatment.
• Physical and Mental Care for Cancer Patients The approach to the care of cancer should include physical and psychological treatment, appropriate diagnosis procedures, education for patients and their families.
• Postoperative Breast Cancer Care The chosen for the paper articles support the implementation of risk reduction strategies for depression in post-operative breast cancer patients.
• Cancer Treatment and Role of Nurses The primary purpose of this paper is to draw attention to current issues related to the treatment of cancer and the role of nurses.
• Ethical Dilemma: Handling a Request for No Further Cancer Treatment Modern technologies can prolong a person’s life and interrupt it, and this is a person’s choice of which decision to make.
• The Importance of Nutrition in Cancer Prevention In the last few decades, the role that diet and nutrition play in the development, progress, and management of cancer has become an important area of study.
• Bilateral Mastectomy for Breast Cancer Prevention One of the options for preventing the development of breast cancer is a bilateral mastectomy. But it may not be a good preventive choice for genetic markers of breast cancer.
• Social Determinants of Health and Cancer A larger population of the black community suffering from cancer loses their lives while receiving treatment at the hospital due to failed cancer care.
• Health Promotion to Reduce Lung Cancer: Grant Proposal Template The project aims to reduce the rate of lung cancer infection and deaths among Aboriginal and Torres Strait Islander people in South Australia.
• Breast Cancer: Pathophysiology, Types and Treatment Breast cancer is a common malignant neoplastic disease in women and mostly develops in the stage of women postmenopausal.
• Pancreatic Cancer: Symptoms and Treatment Treatment is complicated by the fact that pancreatic cancer often does not cause any symptoms until it reaches a large size or does not spread to other tissues.
• Cervical Cancer: Pathophysiological Processes Cervical cancer is a serious disease that may take human lives in a short period of time because its signs and symptoms are not always easily recognized.
• Cervical Cancer Screening Methodology This paper reviews cervical cancer screening methodology and provides a rationale for applying each recommendation to a specific group of the population.
• Physical Activity and Cancer Prevention Physical activity (PA) has to be efficient in preventing cancer, evading cancer repetition, and increasing good results.
• Post-operative Breast Cancer Patients With Depression: Annotated Bibliography This paper is an annotated bibliography about risk reduction strategies at the point of care: Post-operative breast cancer patients who are experiencing depression.
• Skin Cancer Prevention in Australia Skin cancer, or melanoma, is the abnormal behavior of skin cells that is mainly caused by prolonged exposure of unprotected skin to ultraviolet rays.
• Addressing Cancer: The Nursing Process Nurses must use as much information and resources as possible to offer the highest-quality patient-oriented care.
• Wellness Programs for Colorectal Cancer In this plan, the researcher intends to give a clear intervention plan that can help address the problem of colorectal cancer that has affected so many elderly people in our society.
• Epidemiology of Breast Cancer in UK As of 2011, the incidences of breast cancer have been increasing continuously over forty years. Also, there was a general reduction in the rate of mortality caused by breast cancer.
• Deathography of Cancer From an early age, children get to learn about relatives and friends who have passed away and who passed away during their lifetime.
• A Family Experience of a Child Being Diagnosed With Cancer Family members of a child being diagnosed with cancer have to go through a long and complicated road that regrettably, not always leads to success.
• Cancer Prevalence and Health Care More than 5 million people living today in the US are living with cancer. Sixty three percent of 65 years and above have had cancer.
• Breast Cancer and Effective Medical Treatment The aim of this paper is to characterize breast cancer and to describe the modern methods of its treatment and prevention.
• Approach to the Care of Cancer This paper discusses cancer, including the approach to cancer care, cancer complications and side effects, and the ways of addressing the side effects.
• Macmillan Cancer Support Organization’s Data-Driven Decision-Making Macmillan Cancer Support Organization’s stakeholders must examine the cancer care workforce and predict how the future ratio might look for strategic management.
• Passive Smoking and Pancreatic Cancer in Women The association between ETS and pancreatic cancer is weak. The pancreatic cancer risk associated is confounded by environmental tobacco smoke exposures.
• Cervical Cancer: Nursing Research and Evidence-Based Practice This essay seeks to discuss the annual cervical cancer screening practice to identify the EBP that can be used to replace it.
• Pain Management Issues in Cancer Patients Pain has a significant effect on the quality of life of cancer patients, their view of the effectiveness of treatment, disease progression, and survival.
• Cancer: Diagnosis and Treatment An effective approach to cancer care should consider both physical and emotional needs that cancer patients have.
• Breast Cancer Screening Promotion The article begins with a brief description of the North Carolina Breast Cancer Screening Program. The program included social-ecological and community organizing approaches to health promotion.
• Bladder Cancer, Its Mortality Trends and Projection One of the current events in epidemiology is conducting an analysis of bladder cancer incidence, mortality trends, and projection.
• Cervical Cancer in the UK Cervical cancer is one of the most common diseases affecting women, and has a significant amount of lethal outcomes.
• Cancer Diagnosis, Complications and Treatment Cancer may be suspected depending on the individual’s symptoms. The symptoms may present themselves during physical examinations or screening tests.
• Conference: Breast Cancer Survival In the medical sphere, cancer studies are one of the most essential and necessary specialties. For millions of cancer patients worldwide, life is a continued fight for survival.
• Colorectal Cancer and Other Cancer Signs and Diagnoses The reasons for increased colorectal cancer rates and decreased cervical cancer rates in Western society may be related to preferred lifestyles.
• Colorectal Cancer Screening and Its Importance Colorectal cancer screening is recommended by the United States Preventive Services Task Force as an effective way to reduce disease-related morbidity and mortality.
• Researching of Cervical Cancer In its initial stages, the cancer process is asymptomatic and is only detected during an extensive gynecological examination.
• Cancer Treatment Process Perceived by Women With Ovarian Cancer The current paper explores how the process of treating ovarian cancer affects the well-being and physical and emotional state of women.
• Smoking and Gender Factors of Lung Cancer The rising prevalence of lung cancer in young females compared to young males is widespread and not entirely explained by gender variations in smoking habits.
• Breast Cancer: Diagnosis and Treatment Recent efforts from medical professionals and interest groups like Breast Cancer Awareness Month facilitate open discussion around breast cancer.
• Drug Repurposing in Cancer Treatment This article examines the concept of drug repurposing in the context of pharmaceutical companies’ innovation policy: the methods and economic feasibility of repurposing drugs.
• Cancer: Disease Specifics and RNA-Based Detection The paper presents the analysis of cancer as one of the most common causes of death. It shows that there are many types of this disease.
• Stomach Cancer: Diagnosis and Treatment Stomach cancer is a malignant neoplasm that develops in the organ’s gastric mucosa cells and first affecting the epithelium and then growing into the stomach tissue.
• Breast Cancer: Diagnostic and Treatment Breast cancer is one of the most common oncology disorders among females. It has a complicated chain of immune reactions and various structures identified histologically.
• Diet, Physical Activity, Obesity and Related Cancer Risk The paper addresses the connection between cancer and physical activity, diet, and obesity in Latin America and the USA. The transitions in dietary practices may be observed.
• Thyroid Cancer as a Public Health Issue Due to the explosion and fire at the Chornobyl Nuclear Power Plant, a huge quantity of radioactive iodine and cesium penetrated the air.
• EBP Guideline for the National Comprehensive Cancer Network The National Comprehensive Cancer Network clinical guidelines are the recognized standard and most synoptic evidence-based practice policies.
• The Ethics of Control Groups in Cancer Research A study is proposed to determine whether women with breast cancer who underwent a mastectomy have a higher rate of survival.
• Health-Related Misconceptions Regarding Antiperspirants and Breast Cancer There is a myth about the use of antiperspirants, especially aluminum-containing ones, as a risk factor for breast cancer.
• Esophageal Cancer: Description, Population Affected, and Prognosis In esophageal cancer, malignant cells develop in the esophagus tissues, leading to tumor formation; it accounts for 1% of all malignancies diagnosed in the USA each year.
• Diet, Physical Activity, Obesity, and Related Cancer Risk One’s health is affected by their lifestyle, which should be well managed since childhood to set a basis for a healthier adulthood.
• The Cancer Trial: Useful Medical Tool A cancer trial is a tool that helps medical professionals examine and trace the illness to develop its background and establish treatment methods.
• Low-Income Men With Prostate Cancer The paper shows the clinical importance of post-treatment prostate cancer. Low-income disadvantaged men face various barriers, including knowledge.
• Cancer Screening Promotion for Middle-Aged Adults Public health policy among middle-aged adults that promotes cancer literacy and the importance of frequent screenings is likely to yield positive results.
• Naturalistic Observation of Couples Coping With Breast Cancer Couples who are suffering with cancer and their spouses’ psychological well-being were explored in study, which focused on the natural setting and substance of dialogues.
• Breast Cancer: Preventive Measures and Support Methods One of the most common types of cancer that women encounter worldwide is breast cancer. This disease was the cause of approximately 570,000 deaths in 2015.
• Health & Medicine: Breast Cancer in XIX Century The disease of breast cancer was a disease of women, which began to be actively noticed from the beginning of the nineteenth century.
• Breast Cancer: Threat to the Patients Cancer is developed from mutations, namely from atypical changes in genes that regulate cell growth and keep them healthy.
• Environmentally and Lifestyle Linked Cancer The paper argues it is critical to clearly understand the causes of cancer to avoid public misinformation that’s why the paper presents etiology and diagnosis of cancer.
• Case Brief on Colon Cancer and Colostomy The paper presents a medical case brief on a 54-year-old patient suffering from colon cancer who had undergone a surgery known as colostomy.
• Cancer Insurance Evaluation An evaluation of what cancer insurance is, what it covers, how it works, the best providers, and how it differs from health insurance can facilitate a better sense of the policy.
• How to Lower your Cancer Risk. Nutrition Action Health Letter Cancer is the abnormal growth of cells. If a person is genetically predisposed to the disease, it can be difficult to avoid getting it.
• Cancer Patients: The Effectiveness of Pain Diary The pain diary assists the cancer patients in pain management by helping them to identify the nature of pain and where it is localized.
• Herceptin and Breast Cancer Treatment Cancer growth is a series of processes that are driven by alterations of genes that bring about the progressive conversion of usual body cells into extremely malignant imitation.
• The Diagnosis and Staging of Cancer The essay describes the diagnosis of cancer. It also highlights three complications associated with cancer. The discussion offers a detailed approach towards better care of cancer.
• American Cancer Society: The Aspects of Melanoma The current paper discusses the aspects of melanoma. It is a type of skin cancer caused by the uncontrolled growth of melanocytes.
• HIV-AIDS, Nutrition and Cancer in Society Patients suffering from HIV/AIDS need to have a perfect schedule for their nutrition. It is important that they watch their diet to boost their immunity.
• Cancer Early Detection, Prevention, and Survivorship in Arab Countries This paper aims to analyze perception, attitudes, and practice towards cancer early detection, prevention, and survivorship in Arab countries and Oman.
• BRCA Gene Mutation and Breast Cancer This study aims to determine how BRCA 1 and BRCA 2 gene mutations contribute to breast cancer, to analyze the role of BRCA1 and BRCA 2 in the restoration of the damaged DNA.
• Public Health Initiative on Prostrate Cancer Among Maryland’s Blacks The primary goal of the public health initiative is to improve the quality of life for all people in the US and reduce the racial prostate cancer disparities.
• Researching of Testicular Cancer Men with undescended testicles are at increased risk of developing testicular cancer. If the undescended testicle is not in the groin but in the abdomen, the risk is even higher
• Lung and Bronchus Cancer in Smoking Americans Among the causes of lung and bronchus cancer, smoking is the first to be distinguished, which is the reason for the vast majority of incidence cases.
• Breast Cancer and Exercise. Article Summary The research study focused on breast cancer survivors in the Rocky Mountain Cancer Rehabilitation Institute (RMCRI) who had already been treated.
• Dental Caries Among Survivors of Childhood Cancer Some professionals considered caries to be one of the long-term health consequences experienced after cancer while others do not support such an idea.
• The Risk Factors of Breast Cancer This paper will throw light upon what breast cancer is all about, the risk factors, the distribution, and determinants of the same.
• A Collaborative Stress Management Initiative for Mothers of Cancer Children The article explored the psychological stress experienced by mothers who have cancerous children. The research is current and relevant to contemporary health issues.
• Multicausality: Reserpine, Breast Cancer, and Obesity All the factors are not significant in the context of the liability to breast cancer development, though their minor influence is undeniable.
• Reducing Cancer Risk With Diet and Lifestyle Change This paper explores the reasons why a strict diet together with changes in lifestyle could significantly reduce the risk of cancer.
• Understanding Epigenetic Mechanisms in Breast Cancer Human cells become cancerous when they undergo genetic modifications that make them acquire growth and multiplication advantages.
• Prostate Cancer Among the Blacks in the State of Maryland Empirical evidence reveals that race or ethnicity is the leading risk factor in the predisposition of men to prostate cancer.
• Breast Cancer: Etiology, Signs and Symptoms Breast cancer is believed to have claimed many human lives in the last four decades, but its prevalence rate has decreased significantly due to improved disease awareness.
• Behavioral Theory: Education Program for Oral Cancer This article uses the social learning theory and the theory of planned behavior to demonstrate the tenets of an effective health education program for the prevention of oral cancer.
• The Epidemiology of Breast Cancer in Young Women The researcher has clearly outlined the essence of the referenced study as aimed at reviewing the epidemiology of breast cancer in young women.
• Factors of Older Adults’ Decision on Cancer Treatment Puts et al. conducted a qualitative study in order to establish the factors that affect the elderly in making a decision to accept or reject cancer treatment.
• Optimal Care For Patients With All Forms of Cancer The nursing profession can benefit from several findings in this study. Optimal care for patients with all forms of cancer can indeed improve the quality of life.
• “Identifying Dietary Patterns Compatible With the Reduction of Cancer Risk” Article Review The review analyzes the purpose of the study aimed at assessing the viability of building healthy eating guidelines in four international settings.
• Processed Meat Consumption Causes Pancreatic Cancer In the United States, more than 30,000 Americans are diagnosed with pancreatic cancer annually, whereas in Europe over 60,000 people suffer from pancreatic cancer yearly.
• Cancer Biology: Oncogenes and Tumor Suppressor Genes This paper seeks to interpret the role oncogenes and tumor suppressors play in transformation during cancer formation.
• Addressing Risk Factors for Lung Cancer Lung cancer cannot be pinpointed to a particular cause. The first prevention measure is ceasing smoking as cigarettes carry chemicals poisonous to the lungs.
• Skin Cancer Types, Cells of Origin Melanoma is the severest form of skin cancer that grows quickly, and it can appear as a spot of a red, brown, black, or grey color with asymmetric sides.
• Genetic Alterations and Cancer The paper will discuss cancer symptoms, causes, diagnosis, treatment, side-effects of treatment, and also its link with a genetic alteration.
• Breast Cancer: Research Review Paper Plenty of scholars’ investigations help doctors, nurses, and patients to take precautionary and care measures to improve their physical and psychological condition.
• Esophageal Cancer and Its Treatment The paper researches the causes of esophageal cancer, its various symptoms, diagnostic, treatment and possible ends.
• Approach to Cancer Care: Diagnosing and Treatment This paper will discuss the process of diagnosing and staging cancer, the complications that are common among patients, and the various treatment remedies available.
• Prostate Cancer Among Blacks in Maryland: Cost-Effectiveness Analysis In the context of the black community in Maryland, the cost-effectiveness analysis portrays the ability of the chosen intervention to minimize the consequences of prostate cancer.
• The Relationship Between Breast Cancer and Genes Cancer, in general, is a disease caused by genes that have mutated or adapted in a different way than was intended.
• Does Marijuana Use and Misuse Cause Cancer? The purpose of this paper is to review two studies that have attempted to define the possible link between marijuana use/misuse and lung cancer.
• Colorectal Cancer Intervention Model The unique skills needed are for successful colorectal cancer intervention includes knowledge of the behavioral challenges, interventions strategies, and health policies.
• How Cancer Affects the Skin? Melanoma represents a type of cancer that affects the melanocytes based in the epidermis section of the skin, and it presents itself as patches of lesions on the skin.
• Functional Characterization of MicroRNAs in Prostate Cancer Prostate cancer is the name given to cancer that starts in the prostate gland. The prostate is a part of the man’s reproductive system and is as big as a walnut.
• Pathology the Respiratory System: Lung Cancer Lung cancer is among the leading causes of death through respiratory illnesses and it has posed a major challenge to the global healthcare system.
• A Perfusion Based 3D Cancer Model for Micro Tumor Formation In vitro perfused 3D cancer model, developed in this thesis, proved valuable for cancer cell culture and related anti-cancer drug tests.
• Breast Cancer Development and Progression: Understanding Epigenetic Mechanisms The development and progression of breast cancer have been attributed to a series of cellular and molecular events, most of which are not well understood.
• Impact of Alcohol Abuse on Breast Cancer Risk in Women This paper will examine the effects of alcohol abuse on the development of breast cancer in women to uncover its devastating consequences.
• Cancer Pain Experiences in Caucasians vs. Minorities Race, age, genetics, cancer type, culture, and psychosocial context have all been shown to impact the manner in which cancer patients experience pain during their illness.
• Cancer Treatment Practice Data Research Evidence-based practice in the nursing profession is fundamental towards effective delivery of care services to patients.
• Effects of Nutrition on Cancer and Cardiovascular Disease Control The high prevalence rate of cancer and heart disease has necessitated the need to underline not only the use of drugs but also the role of nutrition in eradicating cancer.
• Virtual Colonoscopy to Screen for Colon Cancer The aim of this paper is to estimate the technology of virtual colonoscopy from the perspective of several factors, for filling the mentioned gap with the proper amount of arguments.
• African American Women and Cancer The existing disparities regarding healthcare services provision in the United States is a critical issue related to such phenomena as racial and gender discrimination.
• Americcan College of Radiology Protocol and Cancer Therapy Response to Antiangiogenetic Drug Chemotherapy and antiangiogenic drug use are essential in the process of treatment the organs affected with caner cells because the drugs are aimed at reducing the effect of cancer.
• Lung Cancer: Causes and Treatment In the current paper, the crucial peculiarities of lung cancer, as well as the reasons that cause it, will be discussed.
• Approach to Care. Human Cancer Cancer is a group of diseases caused by the uncontrolled division of cells. There is a great variety of cancers, and they are ranked by the type of sell, which the tumor imitates.
• Grant Proposal: Cancel Cancer To ensure that patients diagnosed with cancer can effectively reduce their stress and anxiety levels, a grant is needed to use the program of emotional relief.
• Socioeconomic Factors of Oral Cancer The significant probability of oral cancer being incident in unemployed people was high since the OR (odds ratio) is 2.27.
• Summaries of Three Articles About Lung Cancer One of the most straightforward and efficient ways to understand the pathogenesis of lung cancer is researching the molecular mechanisms that slowly initiate it.
• Cervical Cancer: Symptoms and Treatment Cervical cancer is a condition that affects the cells close to the vagina that can be located in the lower section of the uterus, which is called the cervix.
• Prophylaxis Breast Cancer This paper examines the majority of the parts in detail and considers every risk linked to the development of this dangerous disease.
• Expanded Treatment Options in the Adjuvant Therapy of Colon Cancer Nurses can make a difference in improving survival rates for stage III and IV patients by remaining up to date about treatment options offered by new adjuvant agents.
• Pancreatic Cancer: Diagnostics and Treatment The article analyses the most recent techniques in the diagnosis and management of pancreatic cancer malignancy with a very poor prognosis.
• Nutrition Research With Reference to Colorectal Cancer The present paper is concerned with evaluating the validity and reliability of nutrition research with reference to colorectal cancer.
• Nutritional “Cures” for Clients With Cancer or HIV-AIDS The paper analysis nutrition, which can play a pivotal role in providing some relief to patients especially those with HIV/AIDS.
• Breast Cancer: Analysis and Data Collection The study to determine the quality of health was a qualitative research study because it showed a significant improved in the quality of life for the breast cancer victims.
• Human Patient Simulation for Skin Cancer Prevention Kuhrik et al. conclude that human patient simulation (HPS) can benefit future healthcare providers and promote early prevention and detection.
• The Disease of Breast Cancer: Definition and Treatment Breast cancer is a serious disease during which the breast cells experience abnormal growth. Females usually have a higher risk of developing the disease.
• Cancer and Humor in Children: Approach to Research The paper has discussed the factors that a researcher must consider when planning to investigate the relationship between the sense of humor and hospitalized childhood cancer stressors.
• Synthetic Lethality Approach as Used in Cancer Treatment The essay aims to demonstrate that Synthetic Lethality (SL) is an effective therapy that triggers two mutations in cancer cells that lead to cell death in the result.
• Virtual Colonoscopy – Colon Cancer Screening Virtual Colonoscopy is constantly becoming more and more popular, in comparison with the traditional approach and conventional colonoscopy in particular.
• Genetic Mechanism of Colorectal Cancer Colorectal Cancer (CRC) occurrence is connected to environmental factors, hereditary factors, and individual ones.
• Care of Breast Cancer-Related Lymphoedema The lymphoedema’s clinical manifestations include swelling of the upper or lower extremities, violation of skin nutrition, and subcutaneous fat tissue.
• Lung Cancer among Indigenous Australians A great number of severe diseases are widespread among the Indigenous Australian community. Cancer, especially lung cancer, is one of the most frequent cases.
• Spread of Respiratory Cancer and Ethnicity of the Patient Based on the descriptive statistics, it is possible to study how the spread of respiratory cancer and the ethnicity of the patient are related.
• The Use of Nanotechnology: Cancer Diagnostics and Treatment This article provides an overview of research and presentations on the use of nanotechnology for cancer treatment.
• Cancer: Definition, Epidemiology, and Pain Management Cancer is estimated to reveal itself in as many as 100 types. Statistically, in 2008 the mortality rate from cancer was at the level of 62%.
• Cervical Cancer: Case Study The paper reviews the cervical cancer key determinants, factors to ensure access to prevention technologies, and the trials that the Alliance for Cervical Cancer Prevention faces.
• Women’s Disease: Breast Cancer and Its Consequence Breast cancer is one of the most common cancer types worldwide amounting to 25-30% of all cancer cases detected yearly among women.
• Listing Occupational Carcinogens and Cancer Prevention Occupational carcinogens make up bulk of the known human carcinogens. In the quest to define occupational carcinogens the number of staff exposed is of paramount importance.
• Evidence-Based Clinical Practice Guidelines: Lung Cancer The evidence-based clinical practice guidelines (CPGs) target early detection of lung cancer in patients based on screening tools and techniques suggested by the recent literature.
• Cancer Problem for Today’s Women The critique imposed in the study encompasses the fullness of the knowledge base in medical innovative therapies and pre-caution procedures for women living with cancer.
• Racism in Breast Cancer Treatment Cancer treatment is the least studied field that arises numerous ambiguities and requires a more sophisticated approach in studying.
• Cancer Interference With Dna Replication Reports indicate that a greater percentage of human cancers originate from chemical substances as well as environmental substances.
• Skin Cancer, Its Causes and Preventive Measures Skin cancer is one of the most common of all cancers, therefore, society needs to know the risks involved and must be better educated when it comes to preventative measures.
• Understanding the Skin Cancer Causes and Protecting the Skin Exposure to too much sun can lead to skin cancer. If we do not change our habits majority of us will one time get skin cancer during our lifetime and many people will die from it.
• Cancer and Contemporary Therapeutic Approaches
• Breast Cancer: Discussion of the Problems and Way of Treatment
• Colon Cancer: Possible Treatment Analysis
• Lung Cancer Early Screening in African Americans
• “Preferences for Photographic Art Among Hospitalized Patients With Cancer” the Article by Hanson et al.
• “Preferences for Photographic Art Among Hospitalized Patients With Cancer” the Article by Grossman, A., Schroeter, K., Hanson, A. and Hanson, H.
• “Preferences for Photographic Art Among Hospitalized Patients With Cancer” the Article by Asmus, K., & Grossman, A., Hanson, H. and Schroeter, K.
• “Preferences for Photographic Art Among Hospitalized Patients With Cancer” the Article by Hanson, H., Schroeter, K., Hanson, A., Asmus, K., & Grossman, A.
• Computed Tomography and Related Cancer Risks
• Breast Cancer Epidemiology and Prevention
• Miami Breast Cancer Conference: Scholarly Activity
• Databases in Early Lung Cancer Screening
• Evaluating Intrinsic and Non-Intrinsic Cancer Risk Factors
• Recommendations for Breast Cancer Screening: USPSTF Guidelines
• Factors Influencing Breast Cancer Screening in Low-Income African Americans in Tennessee
• The Approach to the Care of Cancer
• American Cancer Society: Risk Factors, Effective Care and Enhancing Nursing Knowledge
• Cancer: Approach to Care
• American Cancer Society Guidelines Implementation
• “A Culturally Tailored Internet Cancer Support Group for Asian American Breast Cancer Survivors”: Article Analysis
• Lung & Bronchus Cancer Rates in the United States
• Alternative Medicine in Cancer Pain Management
• Cancer Pain Management and Education Programs
• Depression in Female Cancer Patients and Survivors
• Cervical Cancer Intervention in Clinical Practice
• Skin Cancer in Latin American Population
• Breast Cancer and Stress Heightening
• Colorectal Cancer: Factors and Prevention
• Prevention of Breast Cancer
• Reactive Oxygen Species and Cancer Cells Relationship
• Anthem Blue Cross: Breast Cancer Screenings
• Cancer Care, Diagnostics and Complications
• Women’s Healthcare: Breast Cancer Prevention & Treatment
• Cancer Patients and Survivors Support Group
• Colon Cancer Among Male Hispanic Population
• Vomiting and Nausea in Patients with Gastric Cancer
• Benign Prostatic Hyperplasia and Prostate Cancer
• Breast Cancer Inheritance Biophysical Factors
• Gastric Cancer Treatment: Research Instrument
• Cancer Stages, Treatment and Side Effects
• Anxiety and Depression Among Females with Cancer
• Cancer Risk Factors: Biology Concepts
• Mindfulness-Based Music Therapy and Cancer Treatment
• Mammary Cancer: Health Screening Initiative
• Mammography Screening and Breast Cancer Mortality
• Skin Cancer: Examination and Prevention
• Cancer Effects Management Methods
• Cancer Burden and Prevention Strategies
• Mindfulness-Based Therapy for Cancer Patients
• Cervical Cancer Prevention Among British Women
• Breast Cancer Studies: Evaluation and Analysis of Scientific Papers
• Value Care of Cancer
• Community Cancer Screening and Detection Project
• Cancer Care Approaches: Diagnosis, Side Effects, and Treatment
• Music Therapy Effects for Breast Cancer Patients
• Gastric Cancer Treatment: Data Collection
• Cancer: Steps of the Implementation Plan
• Endometrial Cancer Symptoms in Women After 35
• Birth Control Pills and Cervical Cancer Development
• Lung Cancer, Its Etiology Pathophysiology
• Who Work with Cancer Patients?
• Cancer Diagnostics, Staging and Complications
• Breast Cancer: Disease Screening and Diagnosis
• Mindfulness-Based Music Therapy in Cancer Patients
• Prostate Cancer: African American Cancer Initiative
• Cancer Treatment Research: Informed Consent
• Possible Trends in the Cause of Cancer
• Cancer Management: Effective Diagnosis, Treatment, Lessening the Effects of Complications
• Inner Strength in Women Survivors of Cancer
• Approaches to Cancer Care
• From Breast Cancer to Zika Virus – Nursing Issues
• Postmenopausal Women with Breast Cancer
• Tanning Booths and Skin Cancer Relationship – Medicine
• Massage Therapy vs. Simple Touch to Improve Pain and Mood in Patients with Advanced Cancer: A Randomized Trial
• A Research of Breast Cancer Survival
• Can Aspirin Help Reduce the Risk of Lung Cancer?
• What Are the Challenges for Relative Effectiveness Assessment and Early Access of Cancer Immunotherapies in Europe?
• Does Cellular Phone Use Contribute to Cancer Formation?
• Has Medical Innovation Reduced Cancer Mortality?
• Can Diet and Exercise Help Prevent Cancer?
• Does Detecting Breast Cancer with MRIs Increase the Rate of Mastectomies?
• How Are Cancer Cells Structurally Different From Normal?
• Can Elderly Patients With Pancreatic Cancer Gain Survival Advantages Through More Radical Surgeries?
• How Does Cancer Affect Individuals From All Backgrounds?
• Can Immunogenic Chemotherapies Relieve Cancer Cell Resistance to Immune Checkpoint Inhibitors?
• Does Diet Really Help Prevent Colon Cancer?
• Why Do African American Women Contract Breast or Cervical Cancer More Than Any Other Ethnic Group?
• How Does Cancer Form and Spread in the Human Body?
• Can Korean Red Ginseng Increase the Life Span of Cancer Patients?
• Does Natural Killer Cell Deficiency Increase the Risk of Cancer?
• Why Do Women Generally Get Breast Cancer Rather Than Other Cancers?
• Should the Cervical Cancer Vaccine for Girls Be Compulsory?
• Can Religion Help the Healing Process of Cancer?
• Does Green Tea Offer the Prescription for Beating Cancer?
• How Can Nanomedicine Help Cure Cancer?
• What Are the Symptoms and Treatments for Breast Cancer?
• Does Medicare Coverage Improve Cancer Detection and Mortality Outcomes?
• Are Pet Owners Really at Greater Risk of Cancer?
• How Can People Protect Themselves From Cancer?
• Does the Immune System Naturally Protect Against Cancer?
• Understanding cancer: causes, types, and risk factors.
• Complementary and alternative medicine for cancer patients.
• Environmental factors affecting cancer risk.
• The connection between cancer and aging.
• The role of artificial intelligence in cancer diagnosis.
• Strategies for improving quality of life after cancer treatment.
• Precision oncology: how it works.
• The significance of biomarkers in cancer diagnosis and prognosis.
• The role of diet in preventing and managing cancer.
• Ways to reduce cancer risks.
• Breast cancer awareness campaign: causes and prevention.
• Art therapy sessions for cancer patients.
• A healthy eating cookbook for a balanced diet during chemotherapy.
• Inspirational storytelling: collecting personal stories of cancer survivors.
• Raising awareness of the effects of smoking on cancer risk.
• Cancer prevention podcast: interviewing experts.
• Decision-making guide for cancer treatment for patients and their families.
• Surveying the impact of cancer treatment on patients’ daily lives.
• Volunteer-based transportation services for cancer patients.
• A social media campaign for raising awareness about cancer.

Cite this post

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StudyCorgi. (2021, September 9). 271 Cancer Research Topics for Undergraduates and High School Students. https://studycorgi.com/ideas/cancer-essay-topics/

"271 Cancer Research Topics for Undergraduates and High School Students." StudyCorgi , 9 Sept. 2021, studycorgi.com/ideas/cancer-essay-topics/.

StudyCorgi . (2021) '271 Cancer Research Topics for Undergraduates and High School Students'. 9 September.

1. StudyCorgi . "271 Cancer Research Topics for Undergraduates and High School Students." September 9, 2021. https://studycorgi.com/ideas/cancer-essay-topics/.

Bibliography

StudyCorgi . "271 Cancer Research Topics for Undergraduates and High School Students." September 9, 2021. https://studycorgi.com/ideas/cancer-essay-topics/.

StudyCorgi . 2021. "271 Cancer Research Topics for Undergraduates and High School Students." September 9, 2021. https://studycorgi.com/ideas/cancer-essay-topics/.

These essay examples and topics on Cancer were carefully selected by the StudyCorgi editorial team. They meet our highest standards in terms of grammar, punctuation, style, and fact accuracy. Please ensure you properly reference the materials if you’re using them to write your assignment.

This essay topic collection was updated on January 5, 2024 .

Cancer Biology

Focus areas.

The mission of the Department of Cancer Biology is to identify and understand the causes of cancer, to develop innovative approaches to reduce cancer incidence, to create and test novel and more effective therapies, and to translate these findings into clinical care for the benefit of patients.

Research in our department is highly collaborative and is potentiated through close interactions with other basic science departments and translated through clinical collaborations.

Our faculty members are aligned into eight research focus areas that address cancer development, progression and treatment.

Cancer disparities

While cancer affects everyone, certain groups have higher rates of cancer cases, deaths and health complications. These differences can be associated with genetics, sex, racial and ethnic populations, socioeconomic status, or specific geographic areas. Studying the factors that lead to cancer disparities leads to more-effective prevention and treatment approaches for the affected populations.

• Read more about the cancer disparities focus area .

Cancer stem cells

The stem cell theory of cancer proposes that among the many different types of cells within a cancer, there exists a subpopulation of cells called cancer stem cells that multiply indefinitely, are resistant to chemotherapy, and are thought to be responsible for relapse after therapy. Cancer stem cells also give rise to highly metastatic cells that spread to other organs and tissues within the body. A deeper understanding of cancer stem cells is leading to better implementation of existing anti-cancer therapies and identification of new approaches that target the cancer stem cells specifically.

• Read more about the cancer stem cells focus area .

Cancer systems biology

Cancer is a complex disease with many molecular, genetic and cellular causes. Considering these causes as a system of interactions can lead to a better understanding of the processes involved in the development of cancer and response to therapies. Cancer systems biology integrates advanced experimental models, insights from genome sequencing and other large-scale data projects, and computational models to create unified models of cancer behavior.

• Read more about the cancer systems biology focus area .

Oncogenic gene dysregulation and carcinogenesis

Cancer initiates from genetic alterations, including mutations, deletions and copy number gains, that function to activate cancer-promoting pathways or to block processes that normally inhibit cancer development. Through better understanding of pro- and anti-cancer signaling processes and how they become dysregulated in carcinogenesis and tumor progression, our team can improve biological tools for clinicians and devise molecularly targeted therapies to intervene.

• Read more about the oncogenic gene dysregulation and carcinogenesis focus area .

Precision cancer medicine and translational therapeutics

Cancers develop and respond to therapies differently from one patient to the next. A better understanding of the specific processes driving cancer growth and spread in an individual patient allows for tailored therapeutic strategies that are more effective with minimal side effects. Profiling the mutations and abnormalities that drive a tumor, in combination with development of experimental models that assess the specific responses of cancer cells to therapeutics that target those abnormalities, has dramatically improved outcomes in many cancer types.

• Read more about the precision cancer medicine and translational therapeutics focus area .

Tumor immunology and immunotherapy

Therapeutic strategies that stimulate the immune system to target cancer cells can lead to long-lasting tumor regression and minimize relapse. Integrated efforts of laboratory researchers and clinicians are leading to improved knowledge of how the immune system interacts with cancer cells and how immune processes can be intentionally manipulated for therapeutic effect.

• Read more about the tumor immunology and immunotherapy focus area .

Tumor invasion and metastasis

A fundamental property of malignant tumor cells is the ability to invade surrounding tissues and to metastasize to other organs. These abilities underlie the majority of cancer-associated deaths. While invasion and metastasis are often thought of as the final stages of tumor development, recent studies have shown that tumor spread can occur even at early stages of tumor development, sometimes even before the primary tumor has been identified. Development of therapies targeting invasion and metastasis has the promise to significantly reduce cancer mortality.

• Read more about the tumor invasion and metastasis focus area .

Tumor microenvironment

Tumors require complex interactions with surrounding blood vessels, immune cells, supportive tissue structures and cell types that are distinct to the tumor site in order to grow, become invasive and metastasize. Tumors influence their microenvironment by releasing soluble signals that lead to degradation and remodeling of the tissue structures that constrain their growth. Targeting the interactions of tumors with the microenvironment is an important and developing area of study.

• Read more about the tumor microenvironment focus area .

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Cancer Biology Research

Breast cancer cells

The Importance of Cancer Biology Research

Research on the biology of cancer starts with the simplest of questions: What is—and isn’t—normal? To understand how cancer develops and progresses, researchers first need to investigate the biological differences between normal cells and cancer cells. This work focuses on the mechanisms that underlie fundamental processes such as cell growth, the transformation of normal cells to cancer cells, and the spread ( metastasis ) of cancer cells.

Virtually all major advances against cancer originated with discoveries in basic science . Basic research can reveal new ideas about the causes of cancer and how it develops, progresses, and responds to therapy.

Knowledge gained from such studies deepens our understanding of cancer and produces insights that could lead to new clinical interventions. For example, studies of cell signaling pathways  in normal cells and cancer cells have contributed greatly to our knowledge about the disease, revealing molecular alterations that are shared among different types of cancer and pointing to possible treatment strategies.

Decades of basic research in cancer biology have created a broad base of knowledge that has been critical to progress against the disease.

Selected NCI Activities in Cancer Biology Research

NCI Research and the National Cancer Plan

NCI supports a broad variety of research that aligns with the goals of the National Cancer Plan. Read about the plan and explore each goal.

Federal funding for cancer biology is essential because this area of research receives relatively little funding from entities that are driven by profit. NCI supports and directs cancer biology research through a variety of programs and approaches. For example:

• The Metastasis Research Network (MetNet) supports research to improve our understanding of how cancer spreads. Cancer metastasis is a complex, dynamic, nonlinear process. The network supports several specialized centers working collaboratively on multidisciplinary projects focused on several themes of the metastatic process, including mechanisms of early dissemination, cellular and physical microenvironment crosstalk, dormancy, and mechanisms of responses to therapy by metastatic cells.
• The Translational and Basic Science Research in Early Lesions (TBEL) Program is advancing the understanding of the mechanisms driving, or restraining, the development of precancers and early cancers, as well as informing the development of precision prevention approaches. The program supports multidisciplinary research centers that are integrating basic and translational research to investigate the interactions of an early lesion, its microenvironment, and host factors as “co-organizers” of tumor initiation and the development of cancer.
• The Human Tumor Atlas Network is constructing 3-dimensional atlases of the cellular, morphological, and molecular features of human cancers as they evolve from precancerous lesions to advanced disease. The atlases, which represent a diverse patient population, will also be used to study how tumors respond to treatment and develop resistance to drugs.
• The Cancer Tissue Engineering Collaborative (TEC) supports the development and characterization of state-of-the-art biomimetic tissue-engineered technologies for cancer research. This program advances innovative, well-characterized in vitro and ex vivo systems available for cancer research, expands the breadth of these systems to several cancer types, and promotes investigations of cancer with tissue-engineered systems.

NCI Fiscal Year 2025 Professional Judgment Budget Proposal

Each year, NCI prepares a professional judgment budget to lead progress against cancer.

• The consortium of tumor glycomics laboratories and their research partners that make up the Alliance of Glycobiologists for Cancer Research are investigating the cancer-related dynamics of complex carbohydrates. The alliance, which NCI sponsors with the National Institute of General Medical Sciences and the National Heart, Lung, and Blood Institute, aims to study the structure and function of glycans in relation to cancer.
• The NCI RNA Biology Initiative facilitates the exchange of information and expertise among investigator studying the structure, function, and biological roles of RNA for the purpose of developing new cancer diagnostics and therapies.
• NCI’s Centers of Excellence bring together the institute’s intramural researchers to collaborate on new projects and initiatives in various areas of cancer biology, including Chromosome Biology and Genitourinary Malignancies .

Recent Research Findings in Cancer Biology

• Loss of Y Chromosome in Men Makes Bladder Cancer More Aggressive
• Cells’ decision to divide is reversible
• How Fatty Liver Disease Helps Cancer Thrive in the Liver
• No Glucose? Pancreatic Cancer May Have a Ready Energy Alternative
• How Some Brain Tumors Hijack the Mind to Grow
• Researchers discover the multiple shapes of RNA, a boon for drug design
• Vulnerability in Brain Tumors May Open Door to New Treatments
• Preventing Chemo Brain? Study Identifies Potential Approach for Common Problem

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Collection  06 March 2024

Cancer Top 100 of 2023

This collection highlights the most downloaded* cancer research papers published by Scientific Reports in 2023. Featuring authors from around the world, these papers highlight valuable research from an international community.

You can also view the journal's overall Top 100 or the Top 100 within various subject areas . *Data obtained from SN Insights, which is based on Digital Science’s Dimensions.

Severe SARS-CoV-2 infection as a marker of undiagnosed cancer: a population-based study

• Adeline Dugerdil
• Laura Semenzato
• Antoine Flahault

Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years

• Yixian Chen
• Fidela Mushashi
• Rachel A. Murphy

Classification and diagnostic prediction of breast cancer metastasis on clinical data using machine learning algorithms

• Mahendran Botlagunta
• Madhavi Devi Botlagunta
• Mohd Asif Shah

Non-invasive screening of breast cancer from fingertip smears—a proof of concept study

• S. Francese

Combining machine learning with Cox models to identify predictors for incident post-menopausal breast cancer in the UK Biobank

• Xiaonan Liu
• Davide Morelli
• Lei Clifton

Mutational landscape of cancer-driver genes across human cancers

• Musalula Sinkala

Comprehensive liquid biopsy analysis as a tool for the early detection of minimal residual disease in breast cancer

• Dimitra Stergiopoulou
• Athina Markou
• Evi Lianidou

Diagnostic and prognostic potential of the microbiome in ovarian cancer treatment response

• Abigail E. Asangba
• Marina R. S. Walther-Antonio

Tumor organoid biobank-new platform for medical research

The effect of acute exercise on circulating immune cells in newly diagnosed breast cancer patients

• Tiia Koivula
• Salla Lempiäinen
• Ilkka Heinonen

Cancer incidence amongst UK firefighters

• Taylor A. M. Wolffe
• Andrew Robinson
• Anna A. Stec

The optimization of postoperative radiotherapy in de novo stage IV breast cancer: evidence from real-world data to personalize treatment decisions

• Minoru Miyashita
• Onyinye B. Balogun
• Dezheng Huo

Cancer-associated fibroblasts are the main contributors to epithelial-to-mesenchymal signatures in the tumor microenvironment

• Peter M. Szabo
• Saurabh Saha

A model to predict the prognosis of diffuse large B-cell lymphoma based on ultrasound images

• Wenqin Chen

Clustering by antigen-presenting genes reveals immune landscapes and predicts response to checkpoint immunotherapy

• Xutong Gong
• Rachel Karchin

Predicting EGFR mutational status from pathology images using a real-world dataset

• James J. Pao
• Mikayla Biggs
• Lee A. Albacker

Shared hotspot mutations in oncogenes position dogs as an unparalleled comparative model for precision therapeutics

• Lucas Rodrigues
• Joshua Watson
• Shaying Zhao

Polypropylene microplastics promote metastatic features in human breast cancer

• Jun Hyung Park
• Seungwoo Hong
• Hyun Jung Lee

Absolute dosimetry for FLASH proton pencil beam scanning radiotherapy

• Ana Lourenço
• Anna Subiel
• Russell Thomas

Cellular senescence affects energy metabolism, immune infiltration and immunotherapeutic response in hepatocellular carcinoma

Racial disparities in breast cancer treatment patterns and treatment related adverse events

• Nickolas Stabellini
• Jennifer Cullen
• Alberto J. Montero

Fc-competent multispecific PDL-1/TIGIT/LAG-3 antibodies potentiate superior anti-tumor T cell response

Anti-inflammatory effect of combining fish oil and evening primrose oil supplementation on breast cancer patients undergoing chemotherapy: a randomized placebo-controlled trial

• Aleksandra Arsic
• Predrag Krstic
• Vesna Vucic

Incidence and risk of pancreatic cancer in patients with chronic pancreatitis: defining the optimal subgroup for surveillance

• Hyo Suk Kim
• Tae-Geun Gweon
• Jae Hyuck Chang

A 3-month survival model after Gamma Knife surgery in patients with brain metastasis from lung cancer with Karnofsky performance status ≤ 70

• Hangeul Park
• Hyun-Tai Chung
• Eun Jung Lee

A novel facile synthesis of metal nitride@metal oxide (BN/Gd 2 O 3 ) nanocomposite and their antibacterial and anticancer activities

• Mayyadah H. Mohsin
• Khawla S. Khashan
• Ashok Aspatwar

Tubule-U-Net: a novel dataset and deep learning-based tubule segmentation framework in whole slide images of breast cancer

• Çisem Yazıcı

LINE-1 ORF1p as a candidate biomarker in high grade serous ovarian carcinoma

• Michael Gillette
• Ronny Drapkin

CAR-tropic extracellular vesicles carry tumor-associated antigens and modulate CAR T cell functionality

• V. M. Ukrainskaya
• O. E. Musatova
• A. G. Gabibov

Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model

• Nafiseh Moghimi
• Seied Ali Hosseini
• Mohammad Kohandel

Incidence trends and spatial distributions of lung adenocarcinoma and squamous cell carcinoma in Taiwan

• Chun-Ju Chiang
• Wen-Chung Lee

Simultaneous activation of CXC chemokine receptor 4 and histamine receptor H1 enhances calcium signaling and cancer cell migration

• Jin-Woo Lee

Machine learning based combination of multi-omics data for subgroup identification in non-small cell lung cancer

• Seema Khadirnaikar
• Sudhanshu Shukla
• S. R. M. Prasanna

Risk factors for the development of triple-negative breast cancer versus non-triple-negative breast cancer: a case–control study

• Rajesh Dikshit
• Sudeep Gupta

Deep learning for multi-class semantic segmentation enables colorectal cancer detection and classification in digital pathology images

• John-Melle Bokhorst
• Iris D. Nagtegaal
• Francesco Ciompi

Identification of germline cancer predisposition variants in pediatric sarcoma patients from somatic tumor testing

• Piedad Alba-Pavón
• Olatz Villate

E-liquid exposure induces bladder cancer cells to release extracellular vesicles that promote non-malignant urothelial cell transformation

• Ryan D. Molony
• Chia-Hao Wu

Advances in methylation analysis of liquid biopsy in early cancer detection of colorectal and lung cancer

• Hyuk-Jung Kwon
• Sun Hye Shin
• Min Seob Lee

Systematic review of NTRK 1/2/3 fusion prevalence pan-cancer and across solid tumours

• Sophie O’Haire
• Fanny Franchini
• Maarten IJzerman

Pneumonitis associated with pembrolizumab plus chemotherapy for non-squamous non-small cell lung cancer

• Daichi Fujimoto
• Satoru Miura
• Nobuyuki Yamamoto

Efficient breast cancer mammograms diagnosis using three deep neural networks and term variance

• Ahmed S. Elkorany
• Zeinab F. Elsharkawy

Nanosecond pulsed electric field suppresses growth and reduces multi-drug resistance effect in pancreatic cancer

• Wojciech Szlasa
• Olga Michel
• Julita Kulbacka

Termination of trastuzumab in HER2-positive metastatic breast cancer patients who received trastuzumab beyond progression

• Izzet Dogan
• Adnan Aydiner

Survival outcomes of patients with metastatic non-small cell lung cancer receiving chemotherapy or immunotherapy as first-line in a real-life setting

• Yaniss Belaroussi
• Fanny Bouteiller
• Sophie Cousin

Activated T cell therapy targeting glioblastoma cancer stem cells

• Ken Miyaguchi
• Hongqiang Wang

Genomic and molecular landscape of homologous recombination deficiency across multiple cancer types

The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice

• Chenchen Li

Region of interest (ROI) selection using vision transformer for automatic analysis using whole slide images

• Md Shakhawat Hossain
• Galib Muhammad Shahriar
• Suresh Advani

Modeling of intracranial tumor treating fields for the treatment of complex high-grade gliomas

• David J. Segar
• Joshua D. Bernstock
• Sumientra M. Rampersad

Appropriate screening mammography method for patients with breast implants

• Eun Young Ko
• Haejung Kim

Dual blockage of both PD-L1 and CD47 enhances the therapeutic effect of oxaliplatin and FOLFOX in CT-26 mice tumor model

• Reza Alimohammadi
• Ghanbar Mahmoodi Chalbatani
• Seyed Amir Jalali

Targeting BAP1 with small compound inhibitor for colon cancer treatment

• Minhwa Kang
• Seul Gi Park
• Jongbum Kwon

Machine learning-based approaches for cancer prediction using microbiome data

• Pedro Freitas
• Francisco Silva
• Hélder P. Oliveira

Identification of a hypoxia-related gene prognostic signature in colorectal cancer based on bulk and single-cell RNA-seq

• Yihuan Qiao
• Xunliang Jiang

Evaluation of automated techniques for extraction of circulating cell-free DNA for implementation in standardized high-throughput workflows

• Sarah Lehle
• Julius Emons
• Hanna Huebner

Epigenetic modification of gene expression in cancer cells by terahertz demethylation

• Hwayeong Cheon
• Junho K. Hur
• Joo-Hiuk Son

Breast cancer histopathology image-based gene expression prediction using spatial transcriptomics data and deep learning

• Md Mamunur Rahaman
• Ewan K. A. Millar
• Erik Meijering

The NK cell checkpoint NKG2A maintains expansion capacity of human NK cells

• Meike Kaulfuss
• Juliane Mietz
• Obinna Chijioke

TOR1B: a predictor of bone metastasis in breast cancer patients

• Minh Nam Nguyen
• Salima Akter
• Tae Gyu Choi

An integrative machine learning framework for classifying SEER breast cancer

• P. Manikandan
• C. Ponnuraja

Comparative dosimetric analysis of volumetric modulated arc therapy based craniospinal irradiation plans between Halcyon ring gantry and TrueBeam C-arm linear accelerator

• Biplab Sarkar
• Subhra Snigdha Biswal

Detection of oral squamous cell carcinoma in clinical photographs using a vision transformer

• Tabea Flügge
• Robert Gaudin
• Shankeeth Vinayahalingam

Histone H3-wild type diffuse midline gliomas with H3K27me3 loss are a distinct entity with exclusive EGFR or ACVR1 mutation and differential methylation of homeobox genes

• Pamela Ajuyah
• Chelsea Mayoh
• Dong-Anh Khuong-Quang

Discovery of rafoxanide as a novel agent for the treatment of non-small cell lung cancer

• Tingjun Liu

SLC11A2: a promising biomarker and therapeutic target in ovarian cancer

• Liming Tian
• Guofen Yang

HX009, a novel BsAb dual targeting PD1 x CD47, demonstrates potent anti-lymphoma activity in preclinical models

• Faming Zhang
• Qi-Xiang Li

Circulating cf-miRNA as a more appropriate surrogate liquid biopsy marker than cfDNA for ovarian cancer

• Aoife Ward Gahlawat
• Tania Witte
• Sarah Schott

Prediction of pathologic complete response to neoadjuvant systemic therapy in triple negative breast cancer using deep learning on multiparametric MRI

• Zijian Zhou
• Beatriz E. Adrada

Plasma proteome of growing tumors

• Shashi Gupta
• Matthew J. Westacott
• Nebojsa Janjic

High-throughput isolation of cancer cells in spiral microchannel by changing the direction, magnitude and location of the maximum velocity

• Vahid Omrani
• Mohammad Zabetian Targhi
• Reza Nosrati

Engineered E. coli Nissle 1917 for delivery of bioactive IL-2 for cancer immunotherapy

• Sarunas Tumas
• Trine Sundebo Meldgaard
• Morten O. A. Sommer

Identifying molecular targets of Aspiletrein-derived steroidal saponins in lung cancer using network pharmacology and molecular docking-based assessments

• Iksen Iksen
• Wasita Witayateeraporn
• Varisa Pongrakhananon

Antiproliferative effects of mitochondria-targeted N -acetylcysteine and analogs in cancer cells

• Micael Hardy
• Balaraman Kalyanaraman

Epigenetic alterations impede epithelial-mesenchymal transition by modulating centrosome amplification and Myc/RAS axis in triple negative breast cancer cells

• Laxmidhar Das

Targeting mTOR to overcome resistance to hormone and CDK4/6 inhibitors in ER-positive breast cancer models

• María Jimena Rodriguez
• María Cecilia Perrone
• Virginia Novaro

Four-year follow-up on fatigue and sleep quality of a three-armed partly randomized controlled study in breast cancer survivors with cancer-related fatigue

• the CRF study group

GPX4 overexpressed non-small cell lung cancer cells are sensitive to RSL3-induced ferroptosis

• Joo-Won Kim
• Dong Wha Min

Genetic determinants and absence of breast cancer in Xavante Indians in Sangradouro Reserve, Brazil

• Guilherme Bezerra de Castro

Pediatric T-cell acute lymphoblastic leukemia blast signature and MRD associated immune environment changes defined by single cell transcriptomics analysis

• Swati S. Bhasin
• Beena E. Thomas
• Deborah DeRyckere

Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw

• Chin-Yao Shen
• Wei-Pang Chung

A novel 3D culture model for human primary mammary adipocytes to study their metabolic crosstalk with breast cancer in lean and obese conditions

• Marie Rebeaud
• Caroline Bouche
• Catherine Muller

Network pharmacology analysis reveals potential targets and mechanisms of proton pump inhibitors in breast cancer with diabetes

• Hanbin Wang
• Taolan Zhang

Prediction of breast cancer using blood microbiome and identification of foods for breast cancer prevention

• Jeongshin An
• Byung-In Moon

Improving the robustness and stability of a machine learning model for breast cancer prognosis through the use of multi-modal classifiers

• Nikhilanand Arya
• Sriparna Saha
• Snehanshu Saha

Biogenic copper oxide nanoparticles from Bacillus coagulans induced reactive oxygen species generation and apoptotic and anti-metastatic activities in breast cancer cells

• Masoumeh Dolati
• Farzaneh Tafvizi
• Parvaneh Jafari

Effects of the exercise-inducible myokine irisin on proliferation and malignant properties of ovarian cancer cells through the HIF-1 α signaling pathway

• Marziyeh Alizadeh Zarei
• Elahe Seyed Hosseini
• Hossein Nikzad

Potential of bacteriophage therapy in managing Staphylococcus aureus infections during chemotherapy for lung cancer patients

• Huangliang Zheng
• Sharon Shui Yee Leung

Diagnostic ability of deep learning in detection of pancreatic tumour

• M. G. Dinesh
• Nebojsa Bacanin
• Mohamed Abouhawwash

Artificial intelligence-based radiomics for the prediction of nodal metastasis in early-stage lung cancer

• Yoshihisa Shimada
• Norihiko Ikeda

CDCP1 expression is frequently increased in aggressive urothelial carcinoma and promotes urothelial tumor progression

• Miriam Saponaro
• Sina Flottmann
• Abdullah Alajati

Nrf2 inhibition increases sensitivity to chemotherapy of colorectal cancer by promoting ferroptosis and pyroptosis

• Yongzhou Huang
• Wenchang Yang
• Kaixiong Tao

Identification of TP53 mutations in circulating tumour DNA in high grade serous ovarian carcinoma using next generation sequencing technologies

• Leslie Calapre
• Tindaro Giardina
• Elin S. Gray

A comprehensive analysis of PANoptosome to prognosis and immunotherapy response in pan-cancer

• Lingling Zhuang

Meta-analysis of laparoscopic radical hysterectomy, excluding robotic assisted versus open radical hysterectomy for early stage cervical cancer

• Greg Marchand
• Ahmed Taher Masoud
• Malini Govindan

Prognostic impact of PD-L1 and TIGIT expression in non-small cell lung cancer following concurrent chemo-radiotherapy

• Masataka Mori
• Masatoshi Kanayama
• Fumihiro Tanaka

High dose of dexamethasone attenuates docetaxel-induced fluid retention in breast cancer treatment

• Yoshitaka Saito
• Ryota Kanno
• Mitsuru Sugawara

Cytotoxic and chemomodulatory effects of Phyllanthus niruri in MCF-7 and MCF-7 ADR breast cancer cells

• Ola E. Abdel-Sattar
• Rasha Mosa Allam
• Meselhy R. Meselhy

Automatic detection of circulating tumor cells and cancer associated fibroblasts using deep learning

• Siddarth Rawal
• Changhuei Yang

Transcriptional activity mediated by β-CATENIN and TCF/LEF family members is completely dispensable for survival and propagation of multiple human colorectal cancer cell lines

• Janna Fröhlich
• Andreas Hecht

Rewiring of the 3D genome during acquisition of carboplatin resistance in a triple-negative breast cancer patient-derived xenograft

• Mikhail G. Dozmorov
• Maggie A. Marshall
• J. Chuck Harrell

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What Is Chemotherapy and How Does It Work?

Learn more about the basics of chemotherapy, how it works and what to expect.

This article is based on reporting that features expert sources.

How Chemotherapy Works

Getty Images

Hearing the words, “You have cancer,” can be one of the most difficult experiences someone can go through. While processing the gravity of such a diagnosis, it’s natural to wonder what to expect with your treatment plan.

Medical advancements today make it so cancer is often treatable, and recovery is possible. Here are the basics of what to know about chemotherapy, preventative chemotherapy and its side effects.

What Is Chemotherapy?

Chemotherapy is a common treatment for cancer. Since cancer is a condition of uncontrolled and abnormal cell growth in the body, chemotherapy aims to target and destroy these rapidly dividing cells to halt disease progression. In some cases, chemotherapy may administered for non-cancerous autoimmune conditions, like rheumatoid arthritis or lupus .

Many popular chemotherapy drugs, like Doxorubicin and Carboplatin, for example, work by disrupting DNA, preventing cell reproduction and causing cell death.

Various chemotherapy treatments can target different cancers, and often multiple chemotherapy drugs are given in combination with one another, which is called combination therapy. Chemotherapy is commonly given in regular intervals called cycles since it’s hard on the body. During a chemotherapy cycle, cancer cells, along with many healthy cells, die. After the cycle, the body starts to repair healthy cells again, giving time to prepare for another round of chemotherapy.

Chemotherapy drugs can be administered in different ways, such as:

• Orally in pill or capsule form.
• Intravenously, called chemotherapy infusions, which are administered by needle, catheter, port or pump. Port placement requires minor surgery.
• Chemotherapy shots that are injected with a needle.
• Chemotherapy cream or gels that are applied on the skin for certain types of skin cancer.
• Chemotherapy drugs targeted to a specific part of the body. For example, chemotherapy drugs can be given directly in the abdomen, bladder, chest cavity or central nervous system. One form is hyperthermic intraperitoneal chemotherapy. It puts heated chemotherapy in your abdomen after surgery.

A treatment session can take anywhere from a few minutes to a few hours. Some people need a continuous infusion, which can last several days.

Who Needs Chemotherapy?

Chemotherapy is a key treatment option for individuals with cancer. Cancer may be identified through imaging, biopsies, surgeries or pathology reports.

However, surgeons don't always find cancer during an initial investigative operation.

“The rate of undetected, ‘occult’ cancer found on final pathology when no visible cancer is found at the time of surgery has been reported to be as low as 1% and as high as 10%,” says Dr. Aakash Gajjar, a colorectal surgeon at Memorial Hermann Health System in Houston. This is seen sometimes in ovarian cancers , thyroid cancers, brain cancers , pancreatic cancers and other types of gastrointestinal cancers, he adds.

Cancer doctors base their treatment plans, dosage and chemotherapy cycle on evidence-based guidelines, like guidelines from the National Comprehensive Cancer Network. Sometimes doctors may deviate from NCCN guidelines, “if there is new evidence that has not made its way into publication just yet, or if there are new clinical trials available for patients," Gajjar says.

A medical oncologist oversees chemotherapy treatment. These health care providers specialize in chemotherapy and other cancer-fighting drugs.

The type of chemotherapy oncologists would recommend depends on several factors, including:

• Type of cancer.
• Stage of the cancer.
• Aggressiveness of the cancer.
• Molecular and genetic profile of the tumor.
• The patient’s overall health. 
• The patient’s wishes and treatment goals.

Types of Chemotherapy

There are various purposes for chemotherapy.

• Curative chemotherapy : The goal of curative chemotherapy is to rid the body of all cancer cells to achieve complete remission.
• Neoadjuvant therapy : You can think of this treatment as a preparation for the main cancer treatment. The goal of neoadjuvant chemotherapy is to shrink a tumor prior to surgery or radiation.
• Palliative chemotherapy : This treatment aims to improve quality of life by diminishing cancer symptoms, but the goal isn't to rid the body of all the cancer. This is a comfort measure at the end of life, in collaboration with a hospice or palliative care provider.
• Preventative or adjuvant chemotherapy : After treatment of curative intent, like surgery or radiation therapy, preventative chemotherapy is another tool in the arsenal to ensure any lingering cancer dies.

What Is Preventative Chemotherapy?

Preventative chemotherapy is done to decrease the chance of cancer coming back after treatment of curative intent, like surgery to remove the cancer, Dr. Frank Tsai, oncologist and researcher at HonorHealth Research Institute in Scottsdale, Arizona explains. This is also referred to as adjuvant chemotherapy, meaning it’s intended to prevent cancer recurrence.

Doctors typically recommend preventative chemotherapy after a surgery where the cancer is further along, where lymph nodes are involved or the cancer has spread to other organs. Or, if aggressive cancer features are identified later on through tumor testing called biomarker testing, explains Dr. Monique Gary, a breast surgical oncologist and medical director of the Grand View Health cancer program in Sellersville, Pennsylvania. She says cancers that are found at stage zero or in situ, meaning the cancer has not spread, do not require chemotherapy.

Tsai adds, “the first step is to meet with the patient and talk about the plan for chemotherapy. We base this on what type of cancer the patient has, how much benefit preventative chemotherapy has been shown for their cancer, if it improves survival rate, what the side effects are and what the impact will be on their lifestyle."

Preventative chemotherapy is only done in certain cancers where research has shown it to benefit patients, which may include, but are not limited to:

• Breast cancer . 
• Lung cancer.
• Pancreatic cancer.
• Colon cancer.

What Are the Side Effects of Chemotherapy?

Because chemotherapy kills not only the cancer cells but also healthy cells, there are many side effects.

Side effects vary from person to person, says Dr. Misagh Karimi, a medical oncologist at City of Hope Orange County in California.

For example, certain types of chemotherapy – like Oxaliplatin used to treat colon cancer – may cause sensitivity to cold, including chilly weather and cold beverages. Patients experiencing temperature side effects will be advised to avoid icy or cold drinks. Tastes can also change during treatment, and once-favorite foods may seem “off.”

Karimi says some side effects might include:

• Upset stomach.
• Constipation .
• Loss of appetite.
• Neuropathy, which is numbness, tingling or weakness due to nerve damage.
• Sores in the mouth or throat.
• Heart damage.
• Fertility issues. 

To mitigate these symptoms, your doctor may prescribe you medications to counteract some of the symptoms.

To off-set the side effects from chemo, Karimi also suggests:

• Eating a balanced diet of foods that are bland and easy to digest, like oatmeal. Frozen grapes or melon balls are worth a try for mouth sore, if cold sensitivity isn’t an issue.
• Doing gentle exercise, like yoga or walking.
• Drinking plenty of fluids. 

Always follow the advice of your medical provider before trying any home remedies. “For example, we know that some vitamins can make chemotherapy less effective,” Karimi warns.

Long-Lasting and Later-Developing Side Effects of Chemotherapy

Due to the intensity of chemotherapy, there may be lasting or later-developing side effects throughout your life. Prior to receiving chemotherapy, your medical provider will weigh these risks against the risk of your cancer being left untreated, as well as your personal wishes, expected quality of life and prognosis.

According to the National Cancer Institute, some of these risks include:

• Brain or cognitive changes.
• Hormonal changes.
• Eye problems.
• Hearing problems.
• Heart problems.
• Joint changes.
• Lung problems.
• Mouth changes.
• Lymphedema, or swelling of the lymph tissue.
• Changes in mental health, like developing post-traumatic stress disorder due to the hardships of treatment.

The most effective remedy to combat these side effects is to establish a dependable care team. During and after cancer treatment, keep up with your primary care provider, dentist, specialists, audiologists and mental health providers in addition to your cancer doctors. Having regular check-ups and following recommendations from your care team ensures you will maintain the best quality of life possible even after completing treatment.

The Bottom Line

Chemotherapy is a treatment that makes remission and recovery from cancer possible.

With precision oncology, we can look at tumor cells early on and understand how aggressively they may behave in the body. This can help determine the potential benefits of chemotherapy, Gary explains. “It’s important for people of all ages, and in particular younger women, to pay attention to their bodies and understand what is normal to them,” Gary urges. “Do not dismiss your symptoms.”

Frequently Asked Questions

The 7-day rule in chemotherapy is more of a guideline for scheduling chemo cycles. The goal is to balance the killing of cancer cells with giving the body sufficient time to rest and recover. Chemotherapy cycles may be planned in such a way that there will be five days of chemo with two days of rest, all within roughly seven days.

Chemotherapy may be an effective treatment option for many patients. Cancer patients who receive chemotherapy have better overall survival rates than those who have no chemotherapy.

Some chemotherapy drugs can cause painful side effects, such as aching in the muscles and joints, headaches and stomach pains. Pain may be felt as burning, numbness, tingling or shooting pains in the hands and feet (called peripheral nerve damage). This type of pain can last long after treatment ends.

Not necessarily. Some chemotherapy drugs do cause hair loss. Others may cause only hair thinning and some may not cause any hair loss. The reason hair loss sometimes happens is that chemotherapy drugs affect rapidly dividing cells. This describes not only cancer cells, but also those found in the hair follicles, mouth and gastrointestinal tract.

Best Anti-Cancer Foods

Ruben Castaneda and Heidi Godman March 22, 2024

The U.S. News Health team delivers accurate information about health, nutrition and fitness, as well as in-depth medical condition guides. All of our stories rely on multiple, independent sources and experts in the field, such as medical doctors and licensed nutritionists. To learn more about how we keep our content accurate and trustworthy, read our  editorial guidelines .

Gajjar is a colorectal surgeon at Memorial Hermann Health System in Houston.

Gary is a breast surgical oncologist and medical director of the Grand View Health cancer program in Sellersville, Pennsylvania.

Karimi is a medical oncologist at City of Hope Orange County in California.

Tsai is an oncologist and researcher at HonorHealth Research Institute in Scottsdale, Arizona.

Tags: cancer , chemotherapy , oncology , patient advice

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