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New study finds triple-negative breast cancer tumors with an increase in immune cells have lower risk of recurrence after surgery

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By Kelley Luckstein

A new multicenter, international study suggests that people who have early-stage  triple-negative breast cancer  (TNBC) and high levels of immune cells within their tumors may have a lower risk of recurrence and better survival rates even when not treated with chemotherapy. The  study  was published today in the Journal of American Medical Association (JAMA).

TNBC is a breast cancer subtype that does not respond to drugs that target the estrogen receptor or the HER2 protein. It grows rapidly, is more likely to spread beyond the breast before diagnosis and is more likely to recur than other breast cancers. TNBC represents about 15% of all breast cancers and is more common in younger people and in women of African American, Hispanic and Indian descent. Immune cells, also known as tumor-infiltrating lymphocytes, or TILs, are naturally existing immune system cells that can move from the bloodstream into a tumor and can recognize and destroy cancer cells.

"This is an important finding because it highlights that the abundance of TILs in breast tissue is a prognostic biomarker in people with early-stage triple-negative breast cancer, even when chemotherapy is not administered," says  Roberto Leon-Ferre, M.D. , a breast medical oncologist at  Mayo Clinic Comprehensive Cancer Center  and first author of the study. "The study's findings may inspire future clinical trials to explore whether patients with a favorable prognosis (high TILs) can avoid intensive chemotherapy regimens."

"This meta-analysis confirms robustly the prognostic value of TILs that we have previously reported in TNBC patients treated with chemotherapy and expands it to patients treated without chemotherapy," says Sarah Flora Jonas, Ph.D., a statistician at  Gustave Roussy  and co-first author of the study. "Future studies may allow the use of this biomarker along with standard clinicopathological factors to inform treatment decisions in TNBC patients."

"Of interest, the first report suggesting that an increased number of immune cells being associated with better prognosis in breast cancer patients was described by doctors at Mayo Clinic more than 100 years ago," says Roberto Salgado, M.D., co-chair of the International Immuno-Oncology Biomarker Working Group; co-lead of the study; and pathologist from the Peter MacCallum Cancer Centre, Melbourne, Australia, and ZAS Hospitals, Antwerp, Belgium. "It took a global effort and a century later to reexamine this biomarker and bring it closer to application in patient care."

"TILs are not currently measured or reported in the routine examination of tissue samples of breast cancer," says co-senior author,  Matthew Goetz, M.D. , a medical oncologist at Mayo Clinic Comprehensive Cancer Center and the Erivan K. Haub Family Professor of Cancer Research Honoring Richard F. Emslander, M.D. "While prior studies have focused on measuring TILs in people treated with chemotherapy, this is the largest study to comprehensively demonstrate that the presence of TILs influences the natural behavior of breast cancer in people who have surgery and/or radiation with no additional medical treatment."

For this study, Mayo Clinic and Gustave Roussy researchers, in collaboration with the International Immuno-Oncology Biomarker Working Group, led 11 additional groups to collect data on 1,966 participants with early-stage TNBC who only underwent surgery with or without radiation therapy but did not receive chemotherapy. The participants had been followed for a median of 18 years. The results showed that higher levels of TILs in breast cancer tissue were associated with lower recurrence rates among participants with early-stage TNBC.

"Five years after surgery, 95% of participants with small tumors, stage 1 TNBC, and whose tumors had high TILs were alive, compared to 82% of patients whose tumors had low TILs. Importantly, the breast cancer recurrence rate was significantly lower among patients whose tumors had high TILs," says co-senior author,  Stefan Michiels, Ph.D. , head of Oncostat team, Gustave Roussy, Inserm U1018, University Paris-Saclay. "With nearly 2,000 participants involved in the study, we have now assembled the largest international cohort across three continents of people with TNBC in which the primary treatment was surgery without chemotherapy."

"The results of this study could lead to a recommendation to include TILs in the pathology reports of early-stage TNBC worldwide, as it has the potential to inform clinicians and patients when they discuss treatment options," says Dr. Salgado.

Furthermore, this biomarker would only require a visual evaluation by a pathologist looking through a microscope, meaning there are no additional costs associated with identifying the presence of immune cells. This could be particularly beneficial to regions with limited resources, adds Dr. Leon-Ferre.

Most people with early-stage TNBC undergo chemotherapy either before or after surgery, including people with stage 1 breast cancer. Most people receive multiple chemotherapy drugs in combination, which can cause significant side effects. Currently, the main factors considered to determine the course of chemotherapy treatment for each person are the tumor size and whether the cancer has spread to the lymph nodes. However, the authors identified that the number of TILs further influences the risk of future recurrence.

The researchers plan to evaluate TILs as biomarkers in prospective clinical trials evaluating chemotherapy selection based on TIL levels. Ongoing efforts to conduct additional research with other potential biomarkers are underway.

For a complete list of authors, disclosures and funding, see the full paper  here .

Learn more about breast cancer and find a clinical trial at Mayo Clinic.

Join the Breast Cancer Support Group on Mayo Clinic Connect , an online community moderated by Mayo Clinic for patients and caregivers.

Also, read these articles:

• Understanding triple-negative breast cancer and its treatment
• 17-gene signature linked to remission after triple-negative breast cancer treatment

A version of this article was originally published as a press release on the Mayo Clinic News Network .

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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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Home > About the AACR > Newsroom > News Release > AACR Cancer Progress Report Details Exciting Advances in Cancer Research and Treatment

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AACR Cancer Progress Report Details Exciting Advances in Cancer Research and Treatment

Report includes call to action outlining steps congress must take to maintain momentum against cancer for all patients.

PHILADELPHIA – Today, the American Association for Cancer Research (AACR) released the 13th edition of its annual Cancer Progress Report , which chronicles how basic, translational, and clinical cancer research and cancer-related population sciences—primarily supported by federal investments in the National Institutes of Health (NIH) and the National Cancer Institute (NCI)—remain vitally important to improving health and saving lives.

In addition to providing the latest statistics on cancer incidence, mortality, and survivorship, the AACR Cancer Progress Report 2023 offers detailed updates and important context regarding the latest research in cancer etiology, early detection, diagnosis, treatment, prevention, and survivorship. Throughout the report, the personal stories of patients who have benefited from innovative, recently approved anticancer therapeutics highlight the real-world impact of cancer research.

This comprehensive report also features a spotlight on cancer immunotherapy and addresses persistent challenges in cancer research, including cancer disparities, slow progress against certain types of cancer, and the physical, psychosocial, and financial hardships faced by cancer patients, survivors, and their caregivers. A closing call to action outlines steps Congress and other stakeholders must take to ensure that the U.S. maintains its momentum against cancer for the benefit of all patients.

“The advances in cancer research, particularly in the last two decades, have been breathtaking,” said AACR President Philip Greenberg, MD, FAACR, faculty member at Fred Hutchinson Cancer Center. “We are in an era of unparalleled opportunity to make even more breakthroughs for patients. For the cancer research community to achieve these breakthroughs, however, our representatives in Congress must continue to prioritize funding for biomedical research, from basic research to clinical trials. Through the AACR Cancer Progress Report 2023 , we are sharing with the public and policy makers the progress that has been made, how that progress has been delivered to patients, how it’s changed people’s lives, and the unparalleled opportunities that now exist from scientific and technologic advances, so they understand how crucial it is that we maintain this momentum through continued support of NIH and NCI.”

PROMISING TRENDS AND ADVANCES IN CANCER CARE

The medical research community—including researchers in academia and industry, physician-scientists, patient advocates, regulators, and many other stakeholders—has maintained impressive momentum against cancer in recent years. As outlined in the AACR Cancer Progress Report 2023 :

• A new gene therapy-based immunotherapeutic for certain patients with bladder cancer
• A first-in-class antibody drug conjugate for patients with ovarian cancer
• Four new T-cell engaging bispecific antibodies for a range of hematologic malignancies
• The first approval of an immune checkpoint inhibitor for pediatric and adult patients with a rare form of sarcoma
• Due in large part to advances in prevention, early detection, and treatment, the age-adjusted overall cancer death rate in the U.S. fell by 33% between 1991 and 2020— an estimated 3.8 million cancer deaths averted .
• Breast cancer mortality declined by 43% between 1989 and 2020 , leading to an estimated 460,000 fewer breast cancer deaths.
• The decrease in lung cancer mortality has accelerated from 0.9% a year between 1995 and 2005 to nearly 5% a year between 2014 and 2020. This rapid decline is the result of a steep reduction in the U.S. smoking rate as well as the development of numerous highly effective molecularly targeted therapeutics and immunotherapeutics.
• More and better treatment options have led to notable progress against many pediatric cancers as well. Among children (14 and younger) and adolescents (15-19), overall cancer death rates declined by 70% and 64%, respectively, between 1970 and 2020.

THE IMMUNOTHERAPY REVOLUTION

Immunotherapy has revolutionized cancer care. Breakthroughs in this field have contributed to much of the progress noted above, such as declines in the death rates for previously intractable cancers like advanced lung cancer and melanoma. The AACR Cancer Progress Report 2023 contains a spotlight on the history of cancer immunotherapy, the current state of this treatment modality, and the immense promise of the next generation of immunotherapeutics. Highlights include:

• Since 2011, the FDA has approved 11 immune checkpoint inhibitors , which release “brakes” on the surface of certain immune cells—called T cells—so that the T cells are able to destroy cancer cells. Many of these drugs are approved for more than one type of cancer, making immune checkpoint inhibitors a treatment option for 20 cancer types and any tumor with certain specific molecular characteristics.
• Since 2017, the FDA has approved six CAR T-cell therapies to treat a range of hematologic malignancies. CAR T-cell therapy is a type of adoptive cell therapy, which is designed to dramatically increase the number of cancer-killing immune cells a patient has.
• The field is expanding in exciting ways, with researchers combining the power of other cells in the immune system with recent advances in gene editing to develop more personalized and effective versions of adoptive cell therapy for treatment of solid tumors; developing mRNA-based vaccines and therapeutics to treat cancer; and targeting the gut microbiome to increase the efficacy of cancer immunotherapy, among many other innovative approaches.

DESPITE PROGRESS, CHALLENGES PERSIST

Despite the extraordinary scientific progress against cancer in recent years, this complex disease remains a significant threat to human health around the world. In the U.S., it is estimated that nearly 2 million new cases of cancer will be diagnosed and more than 609,000 people will die from the disease in 2023.

Indeed, cancer research and patient care face numerous challenges, as outlined in the AACR Cancer Progress Report 2023 :

• Cancer disparities are a pervasive public health problem, with racial and ethnic minorities and other medically underserved U.S. populations shouldering a disproportionally higher burden of cancer. While advances have been made in identifying, understanding, and addressing some of these disparities, more research and policy solutions are urgently needed to ensure equitable progress against cancer.
• There has been uneven progress against different cancer types. Few treatment options exist for patients diagnosed with pancreatic cancer or glioblastoma, for example, and 5-year relative survival rates for these cancers are extremely low.
• Incidence rates for some cancers are increasing, including for early-onset colorectal cancer, pancreatic cancer, and uterine cancer, in part due to the rising rate of obesity.
• Financial toxicity is widespread, exacerbated by the rising cost of cancer care. In 2019, U.S. cancer patients paid an estimated $16.2 billion in out-of-pocket cancer care costs and lost an additional $5 billion in “time costs.”

FEDERAL FUNDING ESSENTIAL FOR CONTINUED PROGRESS

To confront these and other challenges, the AACR Cancer Progress Report 2023 calls on Congress to support robust, sustained, and predictable annual funding growth for NIH and NCI by providing increases of at least $3.465 billion and $2.6 billion, respectively, in their fiscal year 2024 base budgets. This funding is crucial to continued progress for patients. From 2010 to 2019, NIH funding contributed to the development of 354 out of 356 new drugs, including many cancer drugs, approved by the FDA.

The AACR also urges Congress to:

• Provide $1.7 billion in dedicated funding for Cancer Moonshot activities in FY 2024 across NCI, FDA, and Centers for Disease Control and Prevention (CDC) with the assurance that Moonshot funding will supplement rather than supplant NIH funding in FY 2024.
• Appropriate at least $472.4 million in FY 2024 appropriations for the CDC Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
• Allocate $50 million in funding for the Oncology Center of Excellence at FDA in FY 2024 to allow regulators with the capable staff and necessary tools to conduct expedited review of cancer-related medical products.

“We are proud to release the 13 th annual AACR Cancer Progress Report ,” said AACR CEO Margaret Foti, PhD, MD (hc). “It is our hope that this comprehensive resource will help to increase knowledge about the myriad diseases we call cancer as well as the innovative research that is improving and extending lives. The findings in this report, along with the personal stories of the featured patients, underscore the enormous impact that robust, sustained, and predictable funding for cancer research has had on Americans’ health, and why that support must continue.”

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Scientists study lipids cell by cell, making new cancer research possible

by University of Surrey

Imagine being able to look inside a single cancer cell and see how it communicates with its neighbors. Scientists are celebrating a new technique that lets them study the fatty contents of cancer cells, one by one.

A study led by the University of Surrey has sampled single live cancer cells and measured the fatty lipid compounds inside them. Working with partners at GSK and UCL, and developing new equipment with Yokogawa, the team saw how those cells transformed in response to changes in their environment.

The work appears in Analytical Chemistry .

Dr. Johanna Von Gerichten, from Surrey's School of Chemistry and Chemical Engineering, noted, "The trouble with cancer cells is that no two are alike. That makes it harder to design good treatment, because some cells will always resist treatment more than others. Yet it has always proven tricky to study live cells after they have been removed from their natural environment, in enough detail to truly understand their makeup. That is why it is so exciting to be able to sample live cells under a microscope and study their fatty contents one by one."

Individual pancreatic cancer cells were lifted from a glass culture dish using Yokogawa's Single Cellome System SS2000. This extracts single live cells using tiny tubes 10 µm across—about half the diameter of the thinnest human hair.

By staining the cells with fluorescent dye , the researchers could monitor lipid droplets (stores of fatty molecules inside cells, thought to play an important role in cancer) throughout the experiment.

Then, working with partners at Sciex, researchers developed a new method using a mass spectrometer to fragment the lipids in the cells. This told them about their composition.

The researchers demonstrated that different cells had very different lipid profiles. They also saw how lipids in the cells changed in response to what was going on around them.

"We are really excited to work with scientists from all over the UK to apply this to other types of cells, to better understand infection, immunity and other phenomena as part of our new national facility for single and sub-cellular "omics," SEISMIC," Professor Melanie Bailey said.

"We are also part of an International Atomic Energy Agency program, which is exploring the effects of irradiation on cells. We will be working with researchers from all over the world to understand why some cancer cells resist radiation treatment."

Dr. Carla Newman, Associate Director, Cellular Imaging and Dynamics at GSK, observed, "Our new method paves the way for studying cancer cells in detail we've never seen before. One day, we might be able to see how individual cancer cells communicate with their neighbors. That could unlock new, more targeted treatments. It's great to see universities and industry come together to produce such ground-breaking research."

Journal information: Analytical Chemistry

Provided by University of Surrey

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12 cancer research breakthroughs of 2021

13th December 2021

2021 has been a fantastic year for science with the rollout of the coronavirus vaccine happening at unprecedented speed thanks to the hard work of people around the world. And all through this turbulent time, cancer researchers have been hard at work too. Here’s the 12 big cancer research breakthroughs made by our scientists in 2021.

Diet, obesity and immunotherapy

Our scientists in Spain uncovered how a fat molecule found in palm oil, called palmitic acid, alters the cancer genome, and increases the likelihood cancer will spread . The researchers have started developing therapies that interrupt this process and say a clinical trial could start in the next couple of years.

Researchers in Italy discovered a new way to treat acute leukaemia by engineering immune cells taken from healthy donors and using them to target and destroy blood cancer cells . The team hope this could be the start for a new way to treat leukaemia in the future.

In Spain, researchers made a discovery that could help protect against diet-induced obesity and its related health issues . They found that by blocking a protein present in fatty tissue of obese mice could provide protection from weight gain caused by a high fat diet. Their findings could have major implications for obesity related diseases such as cancer.

Bubbles, brain tumours and preventing bowel cancer

Our scientists in London developed a new way to deliver drugs that can shut down cancer-promoting mutations in neuroblastoma . The findings show that the new delivery method, which uses tiny bubbles to deliver their cargo directly to the tumour cells, could form the basis for a new treatment for this common childhood cancer.

In Ireland, researchers supported by a collaboration between Worldwide Cancer Research and The Brain Tumour Charity discovered how a genetic mutation causes diffuse midline glioma – a childhood brain cancer also known as DIPG. Their discovery shows that it is possible to reverse the effects of the mutation to slow cancer growth.

Researchers in the Netherlands discovered a better understanding of how bowel cancer develops and identified a new way to prevent it. The research has now resulted in a clinical trial that will aim to repurpose a psychiatric drug as a new preventive cancer treatment in a group of people that – without intervention – are virtually 100% likely to develop bowel cancer in their lifetime.

New treatments and clinical trials

Our scientists in France discovered how the tissue surrounding breast cancer tumours can prevent immune cells from reaching and destroying cancer cells . Their findings could lead to better ways to diagnose breast cancer and new ways to improve immunotherapy.

Researchers in Spain co-funded by AECC FC found a potential new way to treat highly aggressive pancreatic cancer . Their findings pave the way to design new treatment combinations that could kill cancer cells while also making them more susceptible to chemotherapy.

We found out that research we funded in 2005 helped to launch clinical trials testing a promising new treatment option for people with bowel cancer . The research revealed how a specific group of immune cells in the body can ‘mask’ the immune responses normally triggered to fight the cancer and have now sparked clinical trials testing a drug that can remove these cells, unmask the immune system, and open the tumour for attack. It’s hoped that this treatment could help prevent the disease from returning and improve survival rates for those with bowel cancer.

Starting new cancer cures

In Argentina, scientists made an exciting new discovery that could lead to the start of new clinical trials for prostate cancer . Their findings reveal a new treatment strategy that helps make immunotherapy work more effectively to kill off the most aggressive types of prostate cancer.

An international study shone a light on the impact the coronavirus pandemic had on the lives of people with liver cancer. Rates of liver cancer in the UK have increased by more than two and a half times since the early 1990s and continue to rise. Liver cancer now affects more than 6,000 people each year in the UK and only about 1 in 8 people survive for 5 years or longer after their diagnosis.

And finally, we were delighted to be able to commit to funding £4.5m on 23 new research projects that will start in 2022! These innovative new ideas from scientists all over the world are crucial for us to end cancer by starting new cancer cures of the future.

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Liver cancer: Molecular signaling pathway of tumor development decoded

Study reveals new starting point for the treatment of hepatocellular carcinoma.

As a malignant disease of the liver cells, hepatocellular carcinoma (HCC) is one of the main causes of cancer-related deaths. While the treatment options for this aggressive type of cancer remain limited, the incidence is increasing. A research team led by Latifa Bakiri and Erwin Wagner from MedUni Vienna’s Clinical Institute for Laboratory Medicine has now described a molecular signalling pathway that plays a key role in the development of liver cancer, thereby identifying a potential new starting point for the development of therapeutic treatments. The results of the study have just been published in the journal Proceedings of the National Academy of Sciences ( PNAS ).

In their research, the international team led by MedUni Vienna, built on earlier study results that had suggested the involvement of certain transcription factors (c-Fos and c-Jun) in the development of hepatocellular carcinomas. Transcription factors are proteins involved in numerous cellular processes, including the control of genes associated with the development of HCC. To advance these findings, the scientists developed a new mouse model.

The experiments carried out with these proteins showed that the combination with previously unexplored (Fra) proteins in this context triggers the cascade of tumour formation. Specifically, this involves the interaction between c-Jun and Fra-2, which the studies showed to be essential in the development of liver cancer. "It is remarkable that we were able to reverse tumour growth by switching off the protein combination of c-Jun and Fra-2," reports the head of the study Erwin Wagner.

The study also showed that tumour growth can be stopped by blocking a specific gene (c-Myc). "Accordingly, our research results suggest that the molecular signalling pathway we have identified represents a promising starting point for further research into HCC and the development of new therapeutic measures," concludes first author Latifa Bakiri.

Hepatocellular carcinoma is an aggressive tumour with rapid progression and limited therapeutic options. Even though the incidence has increased significantly in Western countries in recent decades, this type of cancer is still comparatively rare. However, due to its poor prognosis, HCC is one of the most common causes of cancer-related deaths. HCC occurs in particular in the context of advanced liver disease (cirrhosis, chronic hepatitis B) and is often only diagnosed at a late stage.

• Liver Disease
• Breast Cancer
• Colon Cancer
• Brain Tumor
• Lung Cancer
• Bladder Cancer
• Hepatocellular carcinoma
• Lung cancer
• Breast cancer
• Hepatitis C
• Prostate cancer
• Stomach cancer

Story Source:

Materials provided by Medical University of Vienna . Note: Content may be edited for style and length.

Journal Reference :

• Latifa Bakiri, Sebastian C. Hasenfuss, Ana Guío-Carrión, Martin K. Thomsen, Peter Hasselblatt, Erwin F. Wagner. Liver cancer development driven by the AP-1/c-Jun~Fra-2 dimer through c-Myc . Proceedings of the National Academy of Sciences , 2024; 121 (18) DOI: 10.1073/pnas.2404188121

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10 new breakthroughs in the fight against cancer

Medical advances are continuing to help the world fight cancer. Image:  Unsplash/National Cancer Institute

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This article was originally published in May 2022, and most recently updated in January 2024 .

• Cancer is one of the world’s biggest killers, with around 10 million deaths per year due to the disease.
• Scientists are using artificial intelligence, DNA sequencing, precision oncology and other technologies to improve treatment and diagnosis.
• The Centre for the Fourth Industrial Revolution India, a collaboration with the World Economic Forum, hopes to accelerate 18 cancer interventions.

Cancer kills around 10 million people a year and is a leading cause of death globally, according to the World Health Organization.

Breast, lung and colon cancer are among the most common. Death rates from cancer were falling before the pandemic . But COVID-19 caused a big backlog in diagnosis and treatment .

There is some good news, however. Medical advances are accelerating the battle against cancer. Here are 10 recent developments.

Test to identify 18 early-stage cancers

Researchers in the US have developed a test they say can identify 18 early-stage cancers. Instead of the usual invasive and costly methods, Novelna's test works by analyzing a patient's blood protein. In a screening of 440 people already diagnosed with cancer, the test correctly identified 93% of stage 1 cancers in men and 84% in women. The researchers believe the findings "pave the way for a cost-effective, highly accurate, multi-cancer screening test that can be implemented on a population-wide scale". It's early days, however. With such a small sample screening and a lack of information on co-existing conditions, the test is currently more of "a starting point for developing a new generation of screening tests for the early detection of cancer".

The seven-minute cancer treatment jab

England's National Health Service (NHS) is to be the first in the world to make use of a cancer treatment injection , which takes just seven minutes to administer, rather than the current time of up to an hour to have the same drug via intravenous infusion. This will not only speed up the treatment process for patients, but also free up time for medical professionals. The drug, Atezolizumab or Tecentriq, treats cancers including lung and breast, and it's expected most of the 3,600 NHS patients in England currently receiving it intravenously will now switch to the jab.

Precision oncology

Precision oncology is the “ best new weapon to defeat cancer ”, the chief executive of Genetron Health, Sizhen Wang, says in a blog for the World Economic Forum. This involves studying the genetic makeup and molecular characteristics of cancer tumours in individual patients. The precision oncology approach identifies changes in cells that might be causing the cancer to grow and spread. Personalized treatments can then be developed. The 100,000 Genomes Project, a National Health Service initiative, studied more than 13,000 tumour samples from UK cancer patients , successfully integrating genomic data to more accurately pin-point effective treatment. Because precision oncology treatments are targeted – as opposed to general treatments like chemotherapy – it can mean less harm to healthy cells and fewer side effects as a result.

Artificial intelligence fights cancer

In India, World Economic Forum partners are using emerging technologies like artificial intelligence (AI) and machine learning to transform cancer care. For example, AI-based risk profiling can help screen for common cancers like breast cancer, leading to early diagnosis. AI technology can also be used to analyze X-rays to identify cancers in places where imaging experts might not be available. These are two of 18 cancer interventions that The Centre for the Fourth Industrial Revolution India, a collaboration with the Forum , hopes to accelerate.

Greater prediction capabilities

Lung cancer kills more people in the US yearly than the next three deadliest cancers combined. It's notoriously hard to detect the early stages of the disease with X-rays and scans alone. However, MIT scientists have developed an AI learning model to predict a person's likelihood of developing lung cancer up to six years in advance via a low-dose CT scan. Trained using complex imaging data, 'Sybil' can forecast both short- and long-term lung cancer risk, according to a recent study. "We found that while we as humans couldn't quite see where the cancer was, the model could still have some predictive power as to which lung would eventually develop cancer," said co-author Jeremy Wohlwend.

Clues in the DNA of cancer

At Cambridge University Hospitals in England, the DNA of cancer tumours from 12,000 patients is revealing new clues about the causes of cancer, scientists say. By analyzing genomic data, oncologists are identifying different mutations that have contributed to each person’s cancer. For example, exposure to smoking or UV light, or internal malfunctions in cells. These are like “fingerprints in a crime scene”, the scientists say – and more of them are being found. “We uncovered 58 new mutational signatures and broadened our knowledge of cancer,” says study author Dr Andrea Degasperi, from Cambridge’s Department of Oncology.

Liquid and synthetic biopsies

Biopsies are the main way doctors diagnose cancer – but the process is invasive and involves removing a section of tissue from the body, sometimes surgically, so it can be examined in a laboratory. Liquid biopsies are an easier and less invasive solution where blood samples can be tested for signs of cancer. Synthetic biopsies are another innovation that can force cancer cells to reveal themselves during the earliest stages of the disease.

The application of “precision medicine” to save and improve lives relies on good-quality, easily-accessible data on everything from our DNA to lifestyle and environmental factors. The opposite to a one-size-fits-all healthcare system, it has vast, untapped potential to transform the treatment and prediction of rare diseases—and disease in general.

But there is no global governance framework for such data and no common data portal. This is a problem that contributes to the premature deaths of hundreds of millions of rare-disease patients worldwide.

The World Economic Forum’s Breaking Barriers to Health Data Governance initiative is focused on creating, testing and growing a framework to support effective and responsible access – across borders – to sensitive health data for the treatment and diagnosis of rare diseases.

The data will be shared via a “federated data system”: a decentralized approach that allows different institutions to access each other’s data without that data ever leaving the organization it originated from. This is done via an application programming interface and strikes a balance between simply pooling data (posing security concerns) and limiting access completely.

The project is a collaboration between entities in the UK (Genomics England), Australia (Australian Genomics Health Alliance), Canada (Genomics4RD), and the US (Intermountain Healthcare).

CAR-T-cell therapy

A treatment that makes immune cells hunt down and kill cancer cells was recently declared a success for leukaemia patients. The treatment, called CAR-T-cell therapy, involves removing and genetically altering immune cells, called T cells, from cancer patients. The altered cells then produce proteins called chimeric antigen receptors (CARs). These recognize and can destroy cancer cells. In the journal Nature, scientists at the University of Pennsylvania announced that two of the first people treated with CAR-T-cell therapy were still in remission 12 years on.

Fighting pancreatic cancer

Pancreatic cancer is one of the deadliest cancers. It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years. At the University of California San Diego School of Medicine, scientists developed a test that identified 95% of early pancreatic cancers in a study. The research, published in Nature Communications Medicine , explains how biomarkers in extracellular vesicles – particles that regulate communication between cells – were used to detect pancreatic, ovarian and bladder cancer at stages I and II.

Have you read?

Cancer: how to stop the next global health crisis, how to improve access to cancer medicines in low and middle-income countries, why is cancer becoming more common among millennials, a tablet to cut breast cancer risk.

A drug that could halve the chance of women developing breast cancer is being tested out by England's National Health Service (NHS). It will be made available to almost 300,000 women seen as being at most risk of developing breast cancer, which is the most common type of cancer in the UK . The drug, named anastrozole, cuts the level of oestrogen women produce by blocking the enzyme aromatase . It has already been used for many years as a breast cancer treatment but has now been repurposed as a preventive medicine. “This is the first drug to be repurposed through a world-leading new programme to help us realize the full potential of existing medicines in new uses to save and improve more lives on the NHS," says NHS Chief Executive Amanda Pritchard.

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World Economic Forum articles may be republished in accordance with the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Public License, and in accordance with our Terms of Use.

The views expressed in this article are those of the author alone and not the World Economic Forum.

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Recent developments in cancer research: Expectations for a new remedy

1 Department of Surgery and Science, Kyushu University, Fukuoka Japan

Qingjiang Hu

Yuta kasagi, masaki mori.

Cancer research has made remarkable progress and new discoveries are beginning to be made. For example, the discovery of immune checkpoint inhibition mechanisms in cancer cells has led to the development of immune checkpoint inhibitors that have benefited many cancer patients. In this review, we will introduce and describe the latest novel areas of cancer research: exosomes, microbiome, immunotherapy. and organoids. Exosomes research will lead to further understanding of the mechanisms governing cancer proliferation, invasion, and metastasis, as well as the development of cancer detection and therapeutic methods. Microbiome are important in understanding the disease. Immunotherapy is the fourth treatment in cancer therapy. Organoid biology will further develop with a goal of translating the research into personalized therapy. These research areas may result in the creation of new cancer treatments in the future.

Cancer research has made remarkable progress and new discoveries are beginning to be made. In this review, we will introduce and describe the latest novel areas of cancer research: exosomes, microbiomes, immunotherapy, and organoids.

1. INTRODUCTION

The cancer research field has developed significantly through use of new equipment and technology. One example of new technology is Next‐Generation Sequencing (NGS). Also known as high‐throughput sequencing, NGS is the catch‐all term used to describe a number of different modern nucleic acid sequencing technologies. These methods allow for much quicker and cheaper sequencing of DNA and RNA compared with the previously used Sanger sequencing, and as such have revolutionized the study of genomics and molecular biology. NGS also allows for easier detection of mutations in cancer samples, leading to development of many new agents that can be used to treat patients. For example, if the RAS gene status is detected as wild type in a colorectal cancer patient, then an anti‐EGFR antibody, such as cetuximab or panitumumab, can be used for treatment.

A liquid biopsy, also known as fluid biopsy or fluid phase biopsy, is the sampling and analysis of non‐solid biological tissue, primarily blood. 1 It is being used as a novel way to detect cancer. Like a traditional biopsy, this type of technique is mainly used as a diagnostic and monitoring tool for diseases, and also has the added benefit of being largely noninvasive. Therefore, liquid biopsies can be performed more frequently, allowing for better tracking of tumors and mutations over a duration of time. This technique may also be used to validate the effectiveness of a cancer treatment drug by taking multiple liquid biopsy samples in the span of a few weeks. It may also prove to be beneficial for monitoring relapse in patients after treatment.

Novel devices and drugs have also been developed and used for cancer treatment. For surgery procedures, robotic‐assisted laparoscopic surgery has evolved and made it possible to visualize the fine movement of the forceps in three dimensions. This method is now used in esophageal, gastric, and rectal cancer surgeries in Japan. 2 , 3 , 4

Recently, immunotherapy became an additional method for treating cancer patients. The discovery of the immune checkpoint by Dr Honjo led to the development of immune checkpoint inhibitors. 5 Despite these developments, gastrointestinal cancers are still a major problem in need of new treatment methods. In this review, we introduce and describe four new areas of cancer research that may contribute to cancer treatment in the future: exosomes, microbiome, immunotherapy, and organoids.

2. AN APPLICATION OF EXOSOME RESEARCH IN CANCER THERAPY

An exosome is a small particle that is secreted by cells. Its size can range from 50 to 150 nm and has a surface consisting of proteins and lipids that originate from the cell membrane. Additionally, proteins and nucleic acids, such as DNA, microRNAs, and mRNAs, can be found inside the exosome as its “cargo.” 6 Recently, many researchers have discovered that exosomes are involved in the mechanisms of various diseases. As mentioned above, various functional compounds, such as microRNAs, mRNAs, and proteins, can be contained within exosomes. 7 , 8 Many cells use secretion of exosomes to communicate with one another, and these exosomes can even reach distant cells. Cancer cells can also secrete exosomes that contain molecules beneficial to cancer growth. For example, microRNAs found in cancer exosomes can modulate gene expression to induce angiogenesis in the tumor microenvironment, which supports metastasis. 9 Exosomes released from cancer cells can also reportedly break the blood‐brain barrier, which makes it contribute to brain metastasis. 10 , 11 Cancer cells themselves are similarly affected by the exosomes secreted by the surrounding normal cells. 12 In one case, the exosomes secreted by bone marrow‐delivered mesenchymal stem cells can force cancer cells into a dormant state. 13 These dormant cancer cells become resistant to chemotherapy and are involved in long‐term disease recurrence. Thus, exosomes are deeply involved in cancer proliferation, invasion, and metastasis, as well as in the formation of the tumor microenvironment and pre‐metastatic niche. 13 Further research on cancer‐related exosomes is ongoing.

Knowledge of exosomes can be applied to cancer treatment. If the secretion of exosomes from cancer cells can be prevented, then signal transduction supporting the formation of the tumor microenvironment and pre‐metastatic niche can be blocked. Work focusing on the removal of cancer exosomes is now ongoing. 14

Exosomes can also be utilized for cancer diagnosis. Exosomes secreted by many cell types are found in various body fluids, such as blood and urine. Capturing and analyzing exosomes from cancer cells can be used to detect the presence of disease. 15 Obtaining blood or urine from patients is not very invasive or painful. Since many molecules, such as various proteins, DNA, and microRNAs, can be found in exosomes from normal cells, it is important to distinguish them from cancer‐related ones. If exosomes are to be used for cancer diagnosis, then specific biomarkers need to be discovered. Additionally, the development of a method to detect these exosomes must be done. Currently, exosome detection methods for exosomes abundantly found in the serum of colorectal and pancreatic cancer patients, as well as exosomes found in the urine of bladder cancer patients, are being developed. 16 , 17 Thus, further understanding of the mechanisms governing cancer proliferation, invasion, and metastasis, as well as the development of cancer detection and therapeutic methods, is significantly affected by exosome research.

3. MICROBIOME IN CANCER RESEARCH

A large number of microorganisms inhabit the human body. These microorganisms include bacteria, viruses, and fungi. Among them, bacteria have the most important relationship with the human body. Bacteria can live anywhere within the human body, including the digestive tract, respiratory system, and oral cavity. 18 , 19 , 20 In particular, bacteria in the digestive tract are rich in type and number, 21 with possibly 1000 types and more than 100 trillion individual bacterial cells present. 22 , 23 The overall population of various bacteria found in the human intestine is referred to as the “intestinal flora.” Recently, the terms “microbiota” or “microbiome” have also been widely used.

Recent advancements with NGS have led to a much more precise understanding of the intestinal microbiome. 24 The bacteria in the human microbiome mainly belong to four phyla: Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteri. Of these, Firmicutes and Bacteroidetes are the most dominant species. It is reported that microbiome vary depending on age and race. 25 , 26 Dysbiosis is a condition in which the diversity of the microbiome is reduced. Dysbiosis is reportedly involved in various diseases such as inflammatory bowel disease, colorectal cancer, obesity, diabetes, and allergic diseases. 27 , 28 , 29 For example, bacteria such as Atopobium parvulum and Actinomyces odontolyticus increase in number during the early stages of colorectal cancer (adenomas or intramucosal cancers) and decrease in number during cancer progression. 30 This suggests that a specific microbiome is associated with early stages of colorectal cancer development, which may be useful knowledge for early cancer detection.

Various studies have also been conducted to elucidate the relationship between the microbiome and the human immune system. 31 The IgA antibody, which is one of the most important elements in the intestinal immune system, is believed to play a role in the elimination of pathogens and maintenance of the intestinal environment. The IgA antibody recognizes, eliminates, and neutralizes pathogenic bacteria and toxins. It also maintains a symbiotic relationship by recognizing and binding to the normal microbiome of the host. 32 Mice lacking a microbiome have reduced production of the IgA antibody. A microbiome is required for IgA antibody differentiation. Recent studies have identified W27IgA antibodies that have the ability to bind to various bacteria. 33 Oral administration of a W27IgA antibody to enteritis model mice suppressed enteritis by altering the microbiome. This W27IgA antibody can recognize a part of the amino acid sequence of serine hydroxymethyl transferase, which is a metabolic enzyme involved in bacterial growth. The W27IgA antibody can suppress the growth of E coli by binding to them. However, the W27IgA antibody does not bind to bacteria that suppress enteritis, such as bifidobacteria and lactic acid bacteria. 33 Thus, the microbiome is deeply involved in human intestinal immunity. Recently, it is having been established that the microbiome is not only involved in intestinal immunity, but also in the systemic immune system.

As the analysis of the microbiome progresses, the pathophysiology of various diseases, such as cancers, and its relationship with the regulatory function of the human immune system will be further elucidated. It has been demonstrated that F nucleatum plays a role in the development and progression of colon adenomas and colorectal cancer. It is also related to lymph node metastases and distant metastasis. 34 , 35 Also, microbiome is associated with hepatocellular carcinoma. 36 Studying microbiome will give us some clue in the development and remedy for gastrointestinal cancers (Table  1 ).

Gastrointestinal cancer and their related microbiome

4. THE RISE OF IMMUNOTHERAPY IN CANCER TREATMENT

For many years, surgery, chemotherapy, and radiation therapy were the main methods of cancer treatment. In addition to these therapies, immunotherapy has recently attracted great attention worldwide (Table  2 ). 37 , 38 Under normal circumstances, a cancer antigen will activate the patient's immune system to attack the cancer cells. However, sometimes the immune system does not recognize the cancer cells as non‐self, or it simply fails to attack them. This can result in the development and progression of cancer.

Immune checkpoint inhibitors

Although therapies that activate the immune system against cancer cells have been studied for a long time, the use of the patient's own immune system for cancer treatment was not established. Recently, the effectiveness of both immune checkpoint inhibition therapy and chimeric antigen receptor (CAR)‐T cell therapy has proved to be promising. 39 , 40 Immunotherapy has moved to the forefront of cancer treatment strategies.

There are two major reasons why proving the efficacy of cancer immunotherapies was difficult for some time. First, cancer immunity is strongly suppressed. Signal transduction from immune checkpoint compounds, such as PD‐1 and CTLA4, strongly inhibits cytotoxic T cells (CTLs). 38 This checkpoint mechanism can prevent the immune system from attacking cancer cells. The development of immune checkpoint inhibitors has arisen from the discovery of this mechanism. Inhibition of immune checkpoint molecules with neutralizing antibodies can release the suppression of cancer‐specific CTLs, activate immunity, and promote cancer elimination. The effectiveness of immune checkpoint antibodies has been confirmed and clinically applied to many solid cancers such as melanoma, 41 lung cancer, 42 urothelial cancer, 43 gastric cancer, 44 and esophageal cancer. 45 In addition to PD‐1 and CTLA4, new immune checkpoint molecules, such as LAG3, TIGIT, and SIRPA, are also being actively studied. 46 , 47 , 48 Although this therapy is promising, the cancer cases who respond to these therapies are limited. This is because use of this therapy requires the presence of cancer‐specific CTLs in the patient's body. To maximize the therapeutic effect, it is desirable to select appropriate cases and develop useful biomarkers.

The second difficulty for immunotherapy is that T cells do not recognize specific cancer cell antigens and immune accelerators are too weak. One goal of CAR‐T cell therapy is to strengthen the immune accelerator by administering CTLs to the patient's body that recognize specific cancer cell‐specific antigens. A CAR is prepared by fusing a single chain Fv (scFv), derived from a monoclonal antibody that recognizes a specific antigen expressed by cancer cells, with CD3z and costimulatory molecules (CD28, 4‐1BB, and others). Next, the CAR is introduced to the T cells obtained from a cancer patient and CAR‐T cells are made. CAR‐T cells recognize the specific antigen of the cancer cells and are activated to damage these cells. CAR‐T cells recognize cancer‐specific antigens with high antibody specificity and attack the respective cancer cells with strong cytotoxic activity and high proliferative activity. CAR‐T therapy is effective in blood cancers such as B‐cell acute lymphoblastic leukemia and myeloma. 49 , 50 While CAR‐T cell therapy has a high therapeutic effect, a frequent and serious adverse event called cytokine release syndrome has been observed in some patients. 51 , 52 The development of a technique for suppressing the occurrence of cytokine release syndrome is anticipated. In addition, the development of CAR‐T cell therapies for solid tumors is ongoing.

Recently, there was new progress made in treating gastrointestinal cancer patients. For MSI‐H colorectal cancer, the combination therapy with nivolumab and ipilimumab was approved. From the nivolumab plus ipilimumab cohort of CheckMate‐142, progression‐free survival rates were 76% (9 months) and 71% (12 months); respective overall survival rates were 87% and 85% which were quite high. This new treatment will benefit MSI‐H colorectal cancer patients. 53

Thus, it is expected that further understanding of cancer immune mechanisms and the development of various immunotherapies will contribute to great progress in cancer treatment.

One problem for immunotherapy is that there is no certain predictive biomarker. It was thought that the expression of PD‐1 or PD‐L1 would predict the effect. However, this was not the case. To find a new biomarker, we assessed the cytolytic activity (CYT) score. The CYT score is a new index of cancer immunity calculated from the mRNA expression levels of GZMA and PRF1. We are now evaluating CYT score in gastric cancer patients (data not published). The development in the biomarker search will benefit many gastrointestinal cancer patients.

5. ADVANTAGES FOR USING ORGANOIDS IN CANCER RESEARCH

The three‐dimensional (3D) organoid system is a cell culture‐based, novel, and physiologically relevant biologic platform. 54 An organoid is a miniaturized and simplified version of an organ that is produced in vitro in 3D and shows realistic microanatomy. With only one to a few cells isolated from tissue or cultured cells as the starting material, organoids are grown and passaged in a basement membrane matrix, which contributes to their self‐renewal and differentiation capacities. 54 , 55 The technique used for growing organoids has rapidly improved since the early 2010s with the advent of the field of stem cell biology. The characteristics of stem, embryonic stem cells (ES cells), or induced pluripotent stem cells (iPS cells) that allow them to form an organoid in vitro are also found in multiple types of carcinoma tissues and cells. Therefore, cancer researchers have applied ES cells or iPS cells in their field. 56 , 57 , 58

Organoid formation generally requires culturing stem cells or their progenitor cells in 3D. 54 , 55 The morphological and functional characteristics of various types of carcinoma tissue have been recapitulated in organoids that were generated from single‐cell suspensions or cell aggregates. These suspensions or aggregates were isolated from murine and human tissues or cultured cells, as well as from cancer stem cells propagated in culture. The structures of the organoids show the potential of cancer stem cell self‐renewal, proliferation, and differentiation abilities, and also provide insights into the roles of molecular pathways and niche factors that are essential in cancer tissues. 56 , 57 , 59 , 60 , 61 , 62 The organoid system also has been utilized for studying multiple biological processes, including motility, stress response, cell‐cell communications, and cellular interactions that involve a variety of cell types such as fibroblasts, endothelial cells, and inflammatory cells. These interactions are mediated via cell surface molecules, extracellular matrix proteins, and receptors in the microenvironment under homeostatic and pathologic conditions.

Although the organoid system is a complex and not effortless procedure that requires specific media, supplements, and many tricky techniques, 58 , 63 application of this system has been extended to a variety of cell types from different carcinomas (colorectal, pancreatic, prostate, breast, ovary, and esophageal cancers). 56 , 57 , 59 , 60 , 61 An organoid is generally induced within a few days to weeks, and is faster and less costly than the murine xenograft assay. Furthermore, applying novel genetic manipulations (e.g. CRISPR‐Cas9) can be carried out in the organoid system. 64 , 65

Kasagi et al modified keratinocyte serum‐free medium to grow 3D organoids from endoscopic esophageal biopsies, immortalized human esophageal epithelial cells, and murine esophagi. Esophageal 3D organoids serve as a novel platform to investigate regulatory mechanisms in squamous epithelial homeostasis in the context of esophageal cancers. 64

We anticipate that many experimental results that utilize the organoid system will be published in the future.

The 3D organoid system has emerged in the past several years as a robust tool in basic research with the potential to be used for personalized medicine. 66 By passaging dissociated primary structures to generate secondary 3D organoids, this system can be performed using live tissue pieces obtained from biopsies, operative‐resected specimens, or even frozen tissues. This method has the potential to transform personalized therapy. For example, in the case of cancer recurrence, an effective chemotherapy can be selected by testing the chemotherapeutic sensitivity of cancer‐derived organoids from an individual patient's tissue stocks. In many cases, a patient's organoid accumulation is helpful for testing the sensitivity of novel therapeutic agents for treating carcinoma. 66 Hence, it appears that organoid biology will further develop with a goal of translating the research into personalized therapy.

6. SUMMARY AND FUTURE DIRECTIONS

This review describes four new cancer‐related studies: exosomes, microbiome, immunotherapy, and organoids (Figure  1 ).

The summary of the four cancer research areas. In this figure the summary of the four cancer research areas is shown: exosome, microbiome, immunotherapy, and organoid research

Since exosomes are released in blood or urine, if the capturing system is established, it will be a less invasive test to diagnose cancer. In the present, the presence of circulating tumor DNA (ctDNA) is one of the tools to detect the minimal residual disease. However, since ctDNA is only DNA, it is difficult to spread to cancer research. In that respect, as exosomes include not only DNA but also other nucleic acids and proteins, this will be a new tool for cancer research such as the diagnosis of early cancer.

Microbiome may lead to improved cancer diagnosis and treatment. Detecting a specific microbiome in a gastrointestinal tract may predict a specific cancer. And changing microbiome in some way may result in preventing cancer development.

Organoids may help address the problem of drug resistance, and also lead to the development of personalized therapy. However, producing organoids takes time and testing the drug resistance may take more time. If we could overcome these problems, the research into organoids can contribute to overcoming cancer.

As shown in Table  3 , many new studies and findings are reported into this field of research. These four novel cancer research areas will make many contributions to the diagnosis and treatment of cancer.

Recent studies on exosome, microbiome, immunotherapy, and organoids

Conflict of Interest: All the authors have no conflict of interest to disclose.

ACKNOWLEDGMENTS

We thank Dr Hirofumi Hasuda and Dr Naomichi Koga for their help in preparing this manuscript. We also thank J. Iacona, PhD, from Edanz Group for editing a draft of this manuscript.

Ando K, Hu Q, Kasagi Y, Oki E, Mori M. Recent developments in cancer research: Expectations for a new remedy . Ann Gastroenterol Surg . 2021; 5 :419–426. 10.1002/ags3.12440 [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]

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New study offers hope for a rare and devastating eye cancer

After more than a decade studying a rare eye cancer that produces some of the hardest-to-fight tumors, researchers from University of Pittsburgh Medical Center have found a treatment that works on some patients and, more importantly, a tool that can predict when it is likely to succeed.

The work, published in Nature Communications, is being validated in a clinical trial involving at least 30 patients. It could pave the way for similar methods designed to overcome one of the enduring frustrations of cancer care.

Because tumors differ, not only between patients but even inside the same patient, a treatment that works on one mass may fail on another, even when both are of the same cancer type.

The researchers in Pittsburgh tackled this problem in uveal melanoma, an eye cancer that afflicts only 5 people in a million, but that half the time spreads to other parts of the body, often the liver. The median survival once uveal melanoma has spread has been less than seven months, according to a 2018 study in the journal JAMA Ophthalmology.

“We chose this because it was one of the only cancers that 10 years ago when we started, there was nothing approved for it,” said Udai Kammula, who led the study and directs the Solid Tumor Cell Therapy Program at UPMC Hillman Cancer Center in Pittsburgh.

Scientists had long speculated that the reason uveal melanoma is so tough to fight is that something helps the tumor keep out T cells, a key part of the body’s immune system that develops in bone marrow. However, previous studies by Kammula and his colleagues showed that uveal melanoma tumors actually have T cells inside, and they are turned on.

The problem? The cells lie dormant instead of multiplying and reaching numbers large enough to overwhelm the tumor.

The culprit appears to reside somewhere inside the tumor’s ecosystem of cells, molecules and blood vessels, known formally as the tumor’s “microenvironment.” Kammula compares this ecosystem to the infrastructure that supports a city. Something in that infrastructure helps protect uveal melanoma tumors by preventing the critical T cells from multiplying.

“Ultimately, if we’re going to get rid of cancer, we have to get rid of this infrastructure,” Kammula said.

A tool for predicting success

He and his colleagues have had some success using a treatment known as adoptive cell therapy, which was developed in the 1980s by Steven Rosenberg at the National Institutes of Health.

The treatment involves removing the T cells from the tumor, where they have been unable to proliferate. Scientists then take those T cells and grow them outside the body in a lab dish. They treat patients with chemotherapy to kill off the last of their old immune systems. Finally, they reinfuse the lab-grown T cells into the patient’s blood stream and the cells, now in much greater numbers, go on to attack the tumor.

In this treatment, the T cells are often referred to as tumor-infiltrating leukocytes, or TILs.

Kammula said his team has found that tumors shrink partially or completely in about 35 percent of patients who receive the treatment. But they wanted to know why it doesn’t work in the majority of cases, and whether there might be some way to predict beforehand when it will succeed.

To find out, the researchers analyzed samples from 100 different uveal melanoma tumors that had spread to different parts of the body in 84 patients, seeking to examine all of the tumors’ genetic material.

“We basically put the tumor biopsy in a blender that had the stroma [supportive tissue], the blood vessels, the immune cells, the tumor cells. It had everything,” Kammula said, explaining that they then analyzed all of the tumor’s genetic material.

They found 2,394 genes that could have helped make the tumor susceptible to treatment, some of them genes that experts would regard as “the usual suspects” and others that were unexpected. Using this long list of genes, the scientists searched for characteristics that they shared.

The genes were predominantly involved in helping the body defend itself against viruses, bacteria and other foreign invaders by removing the invaders and helping tissue heal. Kammula and the study’s lead author, Shravan Leonard-Murali, a postdoctoral fellow in the lab, used the different activity levels of these genes to develop a clinical tool.

The tool, known as a biomarker, assigns a score to a uveal melanoma tumor based on the likelihood that it will respond well to the treatment ― removing T cells, growing them outside the body, then reinfusing them.

So far, Kammula said, the biomarker has been “extremely good,” in predicting when the treatment will be effective, though he added, “these findings will need confirmation in the current ongoing clinical trial.”

“I thought it was somewhat of a tour de force, honestly,” said Eric Tran, an associate member of the Earle A. Chiles Research Institute, a division of Providence Cancer Institute in Portland, Ore. Tran did not participate in the study.

He said that while it will be important to validate these results, “I was certainly encouraged by their studies. And from my perspective, I wonder if that sort of strategy can be deployed in other cancers.”

Ryan J. Sullivan, an oncologist at Massachusetts General Hospital and associate professor at Harvard Medical School who was not involved in the study, called the team’s work “timely” and said “it is even more significant that they appear to have a [tool] that appears to predict which patients will benefit.”

The team at UPMC is already investigating possible wider application of both the treatment and the biomarker in a second clinical trial that involves a dozen different cancers.

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Oncologists' meetings with drug reps don't help cancer patients live longer

Sydney Lupkin

Drug companies often do one-on-one outreach to doctors. A new study finds these meetings with drug reps lead to more prescriptions for cancer patients, but not longer survival. Chris Hondros/Getty Images hide caption

Drug companies often do one-on-one outreach to doctors. A new study finds these meetings with drug reps lead to more prescriptions for cancer patients, but not longer survival.

Pharmaceutical company reps have been visiting doctors for decades to tell them about the latest drugs. But how does the practice affect patients? A group of economists tried to answer that question.

When drug company reps visit doctors, it usually includes lunch or dinner and a conversation about a new drug. These direct-to-physician marketing interactions are tracked as payments in a public database, and a new study shows the meetings work. That is, doctors prescribe about five percent more oncology drugs following a visit from a pharmaceutical representative, according to the new study published by the National Bureau of Economic Research this month.

But the researchers also found that the practice doesn't make cancer patients live longer.

"It does not seem that this payment induces physicians to switch to drugs with a mortality benefit relative to the drug the patient would have gotten otherwise," says study author Colleen Carey , an assistant professor of economics and public policy at Cornell University.

For their research, she and her colleagues used Medicare claims data and the Open Payments database , which tracks drug company payments to doctors.

While the patients being prescribed these new cancer drugs didn't live longer, Carey also points out that they didn't live shorter lives either. It was about equal.

The pharmaceutical industry trade group, which is known as PhRMA, has a code of conduct for how sales reps should interact with doctors. The code was most recently updated in 2022, says Jocelyn Ulrich, the group's vice president of policy and research .

"We're ensuring that there is a constant attention from the industry and ensuring that these are very meaningful and important interactions and that they're compliant," she explains.

The code says that if drug reps are buying doctors a meal, it must be modest and can't be part of an entertainment or recreational event. The goal should be education.

Ulrich also points out that cancer deaths in the U.S. have declined by 33 percent since the 1990s , and new medicines are a part of that.