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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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The Nature Portfolio editors who handle cancer primary research, methods, protocols and reviews bring you the latest articles, covering all aspects from disease mechanisms to therapeutic approaches. Collected here you will also find specially curated content, such as collections, focus issues and animations, all ready to be used in presentations and educational materials. You can also find out about the editors handling cancer content, and the journals at Nature Portfolio that publish articles on this topic and how to submit to them.

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Research Articles

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Top Cancer Research Advances at MSK in 2022

Wednesday, December 14, 2022

Researchers at MSK made discoveries about cancer at its most fundamental levels, increasing understanding of the disease and opening the possibility of new therapies.

Researchers at Memorial Sloan Kettering Cancer Center (MSK) continued to make meaningful strides against cancer in 2022. Laboratory studies conducted at the Sloan Kettering Institute (SKI) and across the institution contributed to the global understanding of how cancer arises, grows, and spreads — opening new possibilities for future therapies and treatments.

“To understand a complex disease like cancer, with its many types and forms, you have to investigate it at its most fundamental levels. This work spans fields including genetics, immunology, molecular biology, pharmacology, and many more,” says MSK President and CEO Selwyn M. Vickers, MD, FACS . “What I want everyone to understand is that MSK is as passionate about our research enterprise as we are about providing unparalleled patient care.”

MSK is home to more than 120 research laboratories focused on better understanding every type of cancer. This includes more than 100 labs at SKI, a dedicated experimental research arm within the larger cancer center. MSK scientists are global leaders in the field , publishing their work frequently in leading scientific and medical journals, and presenting it at top national and international conferences.

Here are some of the most exciting discoveries reported over the past year, in chronological order:

A New Type of Immunotherapy Targets Elusive Cancer Cells

Some people don’t respond to cancer treatment using chimeric antigen receptor (CAR) T cells because their cancer cells have very low levels of the targeted protein, or antigen. A team led by SKI physician-scientist Michel Sadelain, MD, PhD , developed a way to engineer highly sensitive T cells that can destroy cancer cells with low antigen levels. These redesigned T cells, called HLA-independent T cell receptor (HIT) T cells, could be effective when conventional CAR T therapies would fail. The team reported this advance in Nature Medicine on January 13, 2022.

Deep Dive Into Genetic Data Yields Metastasis Clues

Can a tumor’s DNA mutations predict whether and when the cancer will spread? A research team led by MSK computational oncologists Francisco Sanchez-Vega, PhD , and Nikolaus Schultz, PhD , analyzed genomic data from 25,000 patients with 50 different types of cancer to find out. The answer, reported February 3, 2022, in Cell , was “No”; however, the six-year investigation provides important new clues about cancer’s ability to metastasize.

A New Twist on an 80-Year-Old Biochemical Pathway

A team of SKI scientists led by cell biologist Lydia Finley, PhD , reported discovering a previously unappreciated metabolic pathway — an alternate version of the famous Krebs/tricarboxylic acid (TCA) cycle. This new version of the TCA cycle allows cells to use the carbons in nutrients to build new cell biomass rather than burn them for energy. The findings, which were reported on March 9, 2022, in Nature , have broad implications for understanding how cells adapt their metabolism to meet changing needs.

Scientists Find Potential New ‘Soldier’ for Cancer Immunotherapy

A team led by SKI immunologist Ming Li, PhD , discovered a new immune cell type that might be weaponized for immunotherapy. The new cells, which the scientists call innate-like T cells, differ in notable ways from the conventional target of many immunotherapies — the cytotoxic (aka “killer”) T cells. The discovery, reported in the April 20, 2022, issue of Nature , raises hopes of narrowing the gap between people who respond to immunotherapy and those who do not.

A Sensor Sniffs for Cancer, Using Artificial Intelligence

MSK researchers, led by Kravis WiSE postdoctoral fellow Mijin Kim, PhD , and SKI biomedical engineer Daniel Heller, PhD , developed an AI-assisted nanosensor that can detect ovarian cancer signals in the blood. Once validated, the test could potentially aid early detection of ovarian cancer, which is urgently needed. The scientists reported the research in the May 12, 2022, issue of Nature Biomedical Engineering .

Finding a New — and Common — Subtype of Prostate Cancer

Scientists at MSK and Weill Cornell Cancer Center identified a previously uncharacterized subtype of hormone-resistant prostate cancer that accounts for about 30% of all cases. The finding, reported in Science on May 27, 2022, could pave the way for targeted therapies for people with this subtype of prostate cancer. The team, led by MSK physician-scientist Yu Chen MD, PhD , a member of the Human Oncology and Pathogenesis Program , used organoids and patient-derived xenografts (cells from tumors implanted into immunodeficient mice) to identify the subtype, which they call stem cell-like (SCL), because some of the genes that are turned on in the cells are reminiscent of those in stem cells.

A Natural Defense Against Viruses Can Lead to Cancer Cell Mutations

APOBEC3 enzymes normally play a role in defending the body from viruses by disrupting their DNA. A research team led by SKI molecular biologist John Maciejowski, PhD , found strong evidence that the enzymes also play a role in causing cancer-related mutations. The discovery was reported in Nature on July 20, 2022.

A Surprising Way for Pancreatic Cancer to Spread

Schwann cells wrap around nerves like insulation around an electric cable. The laboratory of MSK physician-scientist Richard J. Wong, MD, FACS , discovered that Schwann cells organize into tracks, through which pancreatic cancer cells can travel. In addition to blood vessels and the lymphatic system, the Schwann cells represent a third avenue for cancer to spread from the pancreas. As the researchers reported in the August 3, 2022, issue of Cancer Discovery , a protein called c-Jun is key to this process.

SKI Scientists Solve 30-Year-Old Mystery About p53 Protein — Dubbed ‘Guardian of the Genome’

More than half of all cancers have mutations in a gene called p53 , often called the “guardian of the genome.” Cells without working p53 are unable to properly repair damaged DNA, leading to a buildup of mutations. A study led by SKI cancer biologist Scott Lowe, PhD , found that loss of p53 is followed by an orderly progression of predictable genetic changes — not genetic chaos, as previously believed. The researchers, who reported this finding in the August 17, 2022, issue of Nature , say that knowing that there are “rules” to the genetic evolution of tumors suggests a different way of thinking about treating them.

MSK Researchers Discover How Cancer Cells Change Identity To Escape Therapies

Some prostate tumor cells completely change their identity to resist drugs. This transformation, known as lineage plasticity, allows cancer cells to convert to a different cell type. Research done in laboratory models and led by physician-scientist Charles Sawyers, MD , and Sloan Kettering Institute computational biologist Dana Pe’er, PhD , identified signaling pathways that, if blocked, resensitize cells to therapy — potentially opening the door to new clinical approaches. The findings are reported in the September 2, 2022, issue of Science .

New MACHETE Technique Slices Into Cancer Genome To Study Copy Number Alterations

MACHETE, a new CRISPR-based technique to study large-scale genetic deletions efficiently in laboratory models, shed new light on a genetic change that contributes to about 15% of all cancers. The finding, reported on December 7, 2022, in Nature Cancer by postdoctoral fellows Kaloyan Tsanov, PhD , and Francisco “Pancho” Barriga, PhD , in the laboratory of SKI cancer biologist Scott Lowe, PhD , might help identify patients likely to respond to immunotherapies.

Shedding Light on Ovarian Cancer Resistance to Immunotherapy

Ovarian cancers have been stubbornly resistant to immunotherapy compared with many other cancers. A study led by computational oncologist Sohrab Shah, PhD , and medical oncologist Dmitriy Zamarin, MD, PhD, found that ovarian cancer is even more complex than previously understood. The teams discovered there are profound differences among tumors of the same high-grade serous subtype and between the different tumor sites within the same patient. They also learned that ovarian tumors develop new mutations to hide from the immune system as they spread. The research, reported on December 14, 2022, in Nature , reveals mechanisms driving resistance, providing an opportunity to find better ways to improve treatments.

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‘Dramatic’ inroads against aggressive brain cancer

Cutting-edge therapy shrinks tumors in early glioblastoma trial

Haley Bridger

Mass General Communications

A collaborative project to bring the promise of cell therapy to patients with a deadly form of brain cancer has shown dramatic results among the first patients to receive the novel treatment.

In a paper published Wednesday in The New England Journal of Medicine, researchers from Mass General Cancer Center shared the results for the first three patient cases from a Phase 1 clinical trial evaluating a new approach to CAR-T  therapy for glioblastoma.

Just days after a single treatment, patients experienced dramatic reductions in their tumors, with one patient achieving near-complete tumor regression. In time, the researchers observed tumor progression in these patients, but given the strategy’s promising preliminary results, the team will pursue strategies to extend the durability of response.

Left: MRI in Participant 3 before infusion. Right: After infusion on day five.

Image courtesy of The New England Journal of Medicine

“This is a story of bench-to-bedside therapy, with a novel cell therapy designed in the laboratories of Massachusetts General Hospital and translated for patient use within five years, to meet an urgent need,” said co-author Bryan Choi , a neurosurgeon at Harvard-affiliated Mass General and an assistant professor at Harvard Medical School. “The CAR-T platform has revolutionized how we think about treating patients with cancer, but solid tumors like glioblastoma have remained challenging to treat because not all cancer cells are exactly alike and cells within the tumor vary. Our approach combines two forms of therapy, allowing us to treat glioblastoma in a broader, potentially more effective way.”

The new approach is a result of years of collaboration and innovation springing from the lab of Marcela Maus , director of the Cellular Immunotherapy Program and an associate professor at the Medical School. Maus’ lab has set up a team of collaborating scientists and expert personnel to rapidly bring next-generation genetically modified T cells from the bench to clinical trials in patients with cancer.

“We’ve made an investment in developing the team to enable translation of our innovations in immunotherapy from our lab to the clinic, to transform care for patients with cancer,” said Maus. “These results are exciting, but they are also just the beginning — they tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease. We haven’t cured patients yet, but that is our audacious goal.”

CAR-T (chimeric antigen receptor T-cell) therapy works by using a patient’s own cells to fight cancer — it is known as the most personalized way to treat the disease. A patient’s cells are extracted, modified to produce proteins on their surface called chimeric antigen receptors, and then injected back into the body to target the tumor directly. Cells used in this study were manufactured by the Connell and O’Reilly Families Cell Manipulation Core Facility of the Dana-Farber/Harvard Cancer Center.

CAR-T therapies have been approved for the treatment of blood cancers, but the therapy’s use for solid tumors is limited. Solid tumors contain mixed populations of cells, allowing some malignant cells to continue to evade the immune system’s detection even after treatment with CAR-T. Maus’ team is working to overcome this challenge by combining two previously separate strategies: CAR-T and bispecific antibodies, known as T-cell engaging antibody molecules. The version of CAR-TEAM for glioblastoma is designed to be directly injected into a patient’s brain.

In the new study, the three patients’ T cells were collected and transformed into the new version of CAR-TEAM cells, which were then infused back into each patient. Patients were monitored for toxicity throughout the duration of the study. All patients had been treated with standard-of-care radiation and temozolomide chemotherapy and were enrolled in the trial after disease recurrence.

• A 74-year-old man had his tumor regress rapidly but transiently after a single infusion of the new CAR-TEAM cells.
• A 72-year-old man was treated with a single infusion of CAR-TEAM cells. Two days after receiving the cells, an MRI showed a decrease in the tumor’s size by 18 percent. By day 69, the tumor had decreased by 60 percent, and the response was sustained for more than six months.
• A 57-year-old woman was treated with CAR-TEAM cells. An MRI five days after the infusion showed near-complete tumor regression.

The authors note that despite the remarkable responses among the first three patients, they observed eventual tumor progression in all the cases, though in one case, there was no progression for over six months. Progression corresponded in part with the limited persistence of the CAR-TEAM cells over the weeks following infusion. As a next step, the team is considering serial infusions or preconditioning with chemotherapy to prolong the response.

“We report a dramatic and rapid response in these three patients. Our work to date shows signs that we are making progress, but there is more to do,” said co-author Elizabeth Gerstner, a Mass General neuro-oncologist.

In addition to Choi, Maus, and Gerstner, other authors are Matthew J. Frigault, Mark B. Leick. Christopher W. Mount, Leonora Balaj, Sarah Nikiforow, Bob S. Carter, William T. Curry, and Kathleen Gallagher.

The study was supported in part by the National Gene Vector Biorepository at Indiana University, which is funded under a National Cancer Institute contract.

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Cancer research highlights from 2023

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By Mayo Clinic staff

Researchers at Mayo Clinic Comprehensive Cancer Center spent 2023 studying the biology of cancer and new ways to predict, prevent, diagnose and treat the disease. Their discoveries are creating hope and transforming the quality of life for people with cancer today and in the future. Here are some highlights from their research over the past year:

Mayo Clinic researchers link ovarian cancer to bacteria colonization in the microbiome.

A specific colonization of microbes in the reproductive tract is commonly found in people with ovarian cancer, according to a study from the Mayo Clinic  Center for Individualized Medicine . Published in  Scientific Reports  and led by  Marina Walther-Antonio, Ph.D. , a Mayo Clinic researcher, and Abigail Asangba, Ph.D., the discovery strengthens the evidence that the bacterial component of the microbiome — a community of microorganisms that also consists of viruses, yeasts and fungi — is an important indicator for early detection, diagnosis and prognosis of ovarian cancer . The study also suggests that a higher accumulation of pathogenic microbes plays a role in treatment outcomes and could be a potential indicator for predicting a patient's prognosis and response to therapy.  Read more .

Artificial intelligence is forging a new future for colorectal cancer and other digestive system diseases.

Colonoscopy remains the gold standard in detecting and preventing colorectal cancer , but the procedure has limitations. Some studies suggest that more than half of post-colonoscopy colon cancer cases arise from lesions missed at patients' previous colonoscopies. In 2022, Michael Wallace, M.D. , a Mayo Clinic gastroenterologist, published the results  of an international, multicenter study testing the impact of adding artificial intelligence (AI) to routine colonoscopies. His team, including James East, M.D. , a Mayo Clinic gastroenterologist, and other researchers from the U.S., the U.K., Italy, Germany and Ireland, found that incorporating AI into colonoscopies reduced the risk of missing polyps by 50%.  Read more .

A big step forward: Bringing DNA sequencing data to routine patient care.

The Tapestry study , an extensive genomic sequencing clinical research study, aims to complete exome sequencing (sequencing the protein-coding regions of a genome) for 100,000 Mayo Clinic patients. The results will be integrated into patients’ electronic health records for three hereditary conditions, and the amassed data will contribute to a research dataset stored within the Mayo Clinic Cloud on the Omics Data Platform. The overall hope of Tapestry is to accelerate discoveries in individualized medicine to tailor prevention, diagnosis and treatment to a patient's unique genetic makeup. It is poised to advance evidence that exome sequencing, when applied to a diverse and comprehensive general population, can proficiently identify carriers of genetic variants that put them at higher risk for a disease, allowing them to take preventive measures.  Read more .

Patients with multiple tumors in one breast may not need a mastectomy.

Patients who have multiple tumors in one breast may be able to avoid a mastectomy if surgeons can remove the tumors while leaving enough breast tissue, according to research led by the  Alliance in Clinical Trials in Oncology  and  Mayo Clinic Comprehensive Cancer Center . Patients would receive breast-conserving therapy — a  lumpectomy  followed by whole-breast  radiation therapy — rather than mastectomy . The study is published in the  Journal of Clinical Oncology . Historically, women with multiple tumors in one breast have been advised to have a mastectomy. Now, patients can be offered a less invasive option with faster recovery, resulting in better patient satisfaction and cosmetic outcomes, says  Judy Boughey, M.D. , lead author, Mayo Clinic breast surgical oncologist and the W.H. Odell Professor of Individualized Medicine. Read more .

Staging pancreatic cancer early with minimally invasive surgery shows positive results in patient prognosis.

A study published in the  Journal of the American College of Surgeons  reveals that performing a minor surgical procedure on patients newly diagnosed with  pancreatic cancer  helps to identify cancer spread early and determine the stage of cancer. The researchers add that the surgery ideally should be performed before the patient begins chemotherapy. "This is an important study because it supports that staging laparoscopy may help determine a patient's prognosis and better inform treatment so that patients avoid unhelpful or potentially harmful surgical therapy," says  Mark Truty, M.D. , a Mayo Clinic surgical oncologist who led the research.  Read more .

Mayo Clinic study reveals proton beam therapy may shorten breast cancer treatment.

In a trial published in  The Lancet Oncology , Mayo Clinic Comprehensive Cancer Center researchers uncovered evidence supporting a shorter treatment time for people with breast cancer . The study compared two separate dosing schedules of pencil-beam scanning proton therapy , known for its precision in targeting cancer cells while preserving healthy tissue to reduce the risk of side effects. The investigators found that both 25-day and 15-day proton therapy schedules resulted in excellent cancer control while sparing surrounding non-cancerous tissue. Further, complication rates were comparable between the two study groups. "We can now consider the option of 15 days of therapy for patients based on the similar treatment outcomes observed," says  Robert Mutter, M.D. , a Mayo Clinic radiation oncologist and physician-scientist. Read more .

Harnessing the immune system to fight ovarian cancer.

Mayo Clinic research is biomanufacturing an experimental, cell-based ovarian cancer vaccine and combining it with immunotherapy to study a "one-two punch" approach to halting ovarian cancer progression. This research begins with a blood draw from people with advanced  ovarian cancer  whose tumors have returned after standard surgery and chemotherapy. White blood cells are extracted from the blood, biomanufactured to become dendritic cells and returned to the patient. Dendritic cells act as crusaders that march through the body, triggering the immune system to recognize and fight cancer. "We're building on an earlier phase 1 clinical trial  that showed promising results  in terms of survival after the dendritic cell-based vaccine," says  Matthew Block, M.D., Ph.D. , co-principal investigator and Mayo Clinic medical oncologist. "Of the 18 evaluable patients in the phase 1 study, 11 had cancer return, but seven of them — 40% — have been cancer-free for almost 10 years. We typically expect 90% of patients in this condition to have the cancer return."  Read more .

New gene markers detect Lynch syndrome-associated colorectal cancer.

Researchers from Mayo Clinic Comprehensive Cancer Center and Mayo Clinic Center for Individualized Medicine have discovered new genetic markers to identify Lynch syndrome-associated colorectal cancer with high accuracy. Studies are underway to determine if these genetic markers are in stool samples and, if so, how this could lead to a non-invasive screening option for people with  Lynch syndrome . The research was published in Cancer Prevention Research , a journal of the American Association for Cancer Research. "This is an exciting finding that brings us closer to the reality that clinicians may soon be able to offer a non-invasive cancer screening option to patients with the highest risk of getting cancer," says  Jewel Samadder, M.D. , co-lead author of the paper and a Mayo Clinic gastroenterologist. Read more .

Mayo Clinic prepares to biomanufacture a new CAR-T cell therapy for B-cell blood cancers.

Mayo Clinic research has developed a new type of  chimeric antigen receptor-T cell therapy (CAR-T cell therapy)  aimed at killing B-cell blood cancers that have returned and are no longer responding to treatment. This pioneering technology, designed and developed in the lab of  Hong Qin, M.D., Ph.D. , a Mayo Clinic cancer researcher, killed B-cell tumors grown in the laboratory and tumors implanted in mouse models. The preclinical findings are published in  Cancer Immunology, Immunotherapy . "This study shows our experimental CAR-T cell therapy targets several blood cancers, specifically chronic lymphocytic leukemia," says Dr. Qin. "Currently, there are six different CAR-T cell therapies approved for treatment of relapsed blood cancers. While the results are impressive, not everyone responds to this treatment. Our goal is to provide novel cell therapies shaped to each patient's individual need."  Read more .

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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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A long-awaited cancer treatment reaches patients.

By Erin Wayman

Managing Editor, Print and Longform

13 hours ago

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Thanks to the pandemic, the immune system has gotten a lot of attention. When I think about all the viruses, bacteria and other invaders that the body’s defenses fend off, I’m in awe, even if the nudge of a vaccine is sometimes needed to help mount the counterattack.

This issue’s cover story reminds me of another reason to be in awe: The immune system not only protects against foreign threats but homegrown ones as well. On Page 22, senior writer Meghan Rosen describes a recent breakthrough in wielding the immune system against cancer. Earlier this year, the U.S. Food and Drug Administration approved the first T cell therapy for a solid tumor , sold under the name Amtagvi. To treat advanced melanoma, doctors remove tumor-infiltrating lymphocytes, a type of T cell known as TILs, from a patient’s own tumor and grow these natural cancer killers by the billions in the lab. Then the battalion of T cells is injected into the patient to improve the body’s odds of beating the cancer.

Oncologist Steven Rosenberg of the U.S. National Cancer Institute became intrigued by the body’s potential for fighting cancer in 1968 after encountering a patient whose tumors spontaneously disappeared, presumably due to the immune system. It took decades to go from that kernel of an idea to the new TIL therapy.

Rosenberg’s TIL therapy was an idea ahead of its time. In fact, it’s an idea whose foundation stretches all the way back to antiquity.

Early reports of cancer suddenly going into remission after an infection date back to ancient Egypt. By the 19th century, scientists began to piece together that an awakened immune system might be at play. In 1891, New York City bone surgeon William Bradley Coley put that idea to the test by infecting patients’ tumors with Streptococcus and Serratia bacteria. It appeared to work: Reportedly more than 1,000 patients saw their tumors shrink or even disappear. Many doctors, however, were wary of infecting people with potentially dangerous bacteria. Another concern was that no one really knew how or why Coley’s treatment worked. And so, cancer immunotherapy stalled.

But throughout the 20th century, scientists demystified the immune system (or at least began to; it’s still quite mysterious!). In 1967, for example, the year before Rosenberg’s realization, immunologists discovered the existence of T cells and their role in immunity. In the last decade or so, advances have translated into wins for cancer patients. In 2011, a class of drugs known as checkpoint inhibitors, which keep cancer-fighting immune cells in attack mode, first became available. In 2017, the FDA approved the first cancer treatment that uses genetically engineered T cells from patients, called CAR T-cell therapy. This form of treatment has successfully treated blood cancers, such as leukemia. Now with TIL therapy, solid tumors are a target.

So far, it’s approved only for advanced melanoma, but studies suggest TIL therapy may work against other kinds of solid tumors too. We’re far from the end of the story, with many lingering questions about how the immune system fights cancer. One big question: Why do therapies often work for some patients but not others? As answers come in, we’ll keep you updated.

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Genetic testing advances help women with high risk of breast cancer avoid surgery

by Vittoria D'Alessio, Horizon: The EU Research & Innovation Magazine

Researchers are discovering new genes linked to breast cancer and refining evaluation of risk to help spare women from life-changing surgery.

They call it the Angelina Jolie effect: the popular belief that only a preventative double mastectomy can safeguard a woman from developing a tumor if she carries gene mutations linked to breast cancer.

Celebrity actress Jolie made headlines in 2013 when she underwent radical breast surgery after genetic testing revealed she carried a gene—BRCA1—that significantly increased her odds of developing breast and/or ovarian cancer .

Fast forward a decade and eight more genes known to raise a woman's susceptibility to breast cancer have been discovered. Among these are BRCA2, which also greatly increases the chances of developing breast cancer, and four genes discovered by BRIDGES, an international research project.

Thanks in large part to groundbreaking work by researchers, prophylactic surgery is no longer seen as inevitable for a woman to stay healthy if she carries a gene that increases her risk of breast cancer.

In parallel to these discoveries, medical understanding of risk—the likelihood of a woman developing breast cancer if she carries specific mutations—has also evolved significantly.

Avoiding surgery where possible

Greater clarity around the level of risk and the treatment options available is welcomed by women 's cancer support groups.

"The ideal outcome of genetic screening is for women to get an accurate picture of their risk and be offered a personalized approach to tumor prevention," said Marzia Zambon, executive director of Europa Donna, Europe's largest breast cancer advocacy group.

"We're pushing for genetic testing to always be done with the professional guidance of a genetic counselor. If testing isn't done right, it can cause a lot of stress and an unnecessary escalation of treatment."

Researchers involved in BRIDGES and B-CAST—another research initiative—have made huge advances in showing how both genes, lifestyle and environmental factors influence the risk of breast cancer. These non-genetic factors include a woman's exposure to pollution, excess body weight, breast tissue density, low physical activity, alcohol consumption, exposure to birth control and other hormones, and the number of children born.

"Until recently, genetic testing could identify women carrying genes linked to breast cancer, but estimates of the risk these women were facing were quite imprecise," said Professor Peter Devilee, BRIDGES research coordinator and cancer geneticist at Leiden University in the Netherlands. This matters because imprecise risk evaluation can result in inaccurate treatment advice.

"Women with a family history of breast cancer are being referred to labs for genetic testing, and mutations are being identified, but if you can't translate a result into a fairly precise breast cancer risk, it can lead to improper risk management advice. We wanted to help clinics interpret results properly."

Predicting with precision

In their quest to estimate the risk posed by any given gene mutation more precisely, the BRIDGES researchers sequenced all suspected breast cancer genes in the genomes of 113,000 women. Of these women, half were known to have had a breast cancer diagnosis, while the other half had not.

The genetic profiles of these patients were then crosslinked with data from 20,000 breast tumors analyzed by the B-CAST team. In addition, the B-CAST researchers contributed information about the genetic profiles of patients' close family members and those all-important lifestyle and environmental risks.

The BRIDGES team contributed an added tranche of data on genes that hadn't yet been implicated in breast cancer, but that might affect the risk of developing breast cancer when appearing in a mutated form.

Finally, all this information was combined with the findings of earlier research efforts that had set out to find common DNA variations in the same cohort of women, including COGS, the world's largest project on genome-wide association studies to predict cancer risk.

The result of all this data crunching? The BRIDGES and B-CAST teams were able to make vast improvements to a pre-existing tool that estimates the risk posed by any given gene mutation or combination of mutations.

Named CanRisk, this online tool, available in seven EU languages, is designed to give an expert—usually a clinical geneticist—an accurate estimate of a woman's risk of developing a specific type of tumor. The higher the score, the greater the risk.

The hope is that more women with moderate-to-high risk of breast cancer will be identified early. CanRisk factors in the subtype of cancer linked to each cancer gene or gene combination. This is important as some tumor subtypes are far more dangerous than others and treatment options , as well as likely health outcomes, differ from subtype to subtype.

A handful of European clinics are currently piloting the user-friendly, CE-marked CanRisk tool. The researchers are hopeful that more will come on board in the years ahead.

More choices, better screening

Being informed of an elevated risk of developing breast cancer is important, but what actions should a woman take upon receiving this information?

"Better precision in predicting breast cancer makes it easier for women to make informed choices about their bodies and their health," said Dr. Marjanka Schmidt, B-CAST coordinator and an epidemiologist with expertise in breast cancer genetics based in the Netherlands. "Ultimately, it cuts overtreatment and reduces the incidence of unnecessary, life-changing surgery."

Typically, women who are identified as at-risk using the CanRisk tool are offered mammograms from an earlier age than other women and/or more frequent mammograms. MRI scans might also be added to their screening protocol.

"CanRisk has brought clear benefits to many, leading to reductions in the occurrence, severity and mortality of breast cancer. And as we continue to refine the tool, it's likely to save more and more lives," said Schmidt, who leads a research group at the Netherlands Cancer Institute and is a professor of genetic epidemiology of (breast) cancer at Leiden University Medical Center.

The research carried out by the BRIDGES and B-CAST teams between 2015 and 2021 has continued.

The B-CAST team is now developing a tool that will help cancer doctors more accurately predict the health benefits of a specific course of treatment for a given woman with a given subtype of breast cancer.

"Some treatments have quite serious side-effects, so it's important for women and clinicians to know how much impact a particular treatment is likely to have on the tumor, and for decisions to be based on the survival benefits of this treatment," said Schmidt.

Meanwhile, the BRIDGES researchers continue in their quest to identify further genes associated with breast cancer.

"We know about 55-60% of the genetic risk factors, but that leaves 40-45% that still need to be discovered," said Devilee.

The combined impact of their research is already being felt. It will continue to help guide both doctors and patients on the best way to decrease both the incidence of breast cancer and the human toll of this disease.

This article was originally published in Horizon the EU Research and Innovation Magazine.

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Important research into thyroid cancer is being done right now in many university hospitals, medical centers, and other institutions around the country. Each year, scientists find out more about what causes the disease, how to prevent it, and how to improve treatment . In past years, for example, evidence has grown showing the benefits of combining surgery with radioactive iodine therapy and thyroid hormone therapy. The results include higher cure rates, lower recurrence rates, and longer survival.

The discovery of the genetic causes of familial (inherited) medullary thyroid cancer now makes it possible to identify family members carrying the abnormal RET gene and to remove the thyroid to prevent cancer from developing there.

Understanding the abnormal genes that cause sporadic (not inherited) thyroid cancer has led to better treatments as well. In fact, treatments that target some of these gene changes are already being used, and more are being developed (see below).

Most thyroid cancers can be treated successfully. But advanced cancers can be hard to treat, especially if they do not respond to radioactive iodine (RAI) therapy. Doctors and researchers are looking for new ways to treat thyroid cancer that are more effective and lead to fewer side effects.

Radioactive iodine (RAI) therapy

Doctors are looking for better ways to see which cancers are likely to come back after surgery. Patients with these cancers may be helped by getting RAI therapy after surgery. Recent studies have shown that patients with very low thyroglobulin levels 3 months after surgery have a very low risk of recurrence even without RAI. More research in this area is still needed.

Researchers are also looking for ways to make RAI effective against more thyroid cancers. For example, in some thyroid cancers, the cells have changes in the BRAF gene, which may make them less likely to respond to RAI therapy. Researchers are studying whether new drugs that target the BRAF pathway can be used to make thyroid cancer cells more likely to take up radioactive iodine. These types of drugs might be useful for people who have advanced cancer that is no longer responding to RAI therapy.

Targeted therapies

In general, thyroid cancers do not respond well to chemotherapy. But exciting data are emerging about some newer targeted drugs . Unlike standard chemotherapy drugs, which work by attacking rapidly growing cells (including cancer cells), these drugs attack specific targets on cancer cells. Targeted drugs may work in some cases when standard chemotherapy drugs do not, and they often have different side effects.

Kinase inhibitors: A class of targeted drugs known as kinase inhibitors may help treat thyroid cancer cells with mutations in certain genes, such as BRAF and RET/PTC . Many of these drugs also affect tumor blood vessel growth.

In many papillary thyroid cancers, the cells have changes in the BRAF gene, which helps them grow. Drugs that target cells with BRAF gene changes, such as vemurafenib (Zelboraf), dabrafenib (Tafinlar), and selumetinib, are now being studied in thyroid cancers with this gene change.

In one study, giving selumetinib to patients with thyroid cancers that had stopped responding to radioactive iodine (RAI) treatment helped make some patients’ tumors respond to treatment with RAI again. It helped patients not only with BRAF mutations, but also with mutations in a different gene called NRAS .

Other kinase inhibitors that have shown early promise against thyroid cancer in clinical trials include sunitinib (Sutent), pazopanib (Votrient), and axitinib (Inlyta).

Some of these other drugs, such as sunitinib, sorafenib, and pazopanib, are already approved to treat other types of cancer, and might be useful against MTC and differentiated thyroid cancers if other treatments are no longer working.

Anti-angiogenesis drugs: As tumors grow, they need a larger blood supply to get enough nutrients. They get it by forming new blood vessels (a process called angiogenesis). Anti-angiogenesis drugs work by disrupting these new blood vessels. Some of the drugs listed above, such as axitinib, sunitinib, and sorafenib, have anti-angiogenic properties.

Another anti-angiogenesis drug being studied for use against thyroid cancer is bevacizumab (Avastin).

Other targeted drugs : The combination of the chemotherapy drug paclitaxel (Taxol) with the targeted drug efatutazone could be helpful in patients with anaplastic thyroid cancer. Efatutazone targets a receptor called PPAR-gamma.

Observation

The chance of being diagnosed with thyroid cancer has risen rapidly in the US in recent years. Much of this rise appears to be the result of the increased use of thyroid ultrasound, which can detect small thyroid nodules that might not otherwise have been found in the past.

Recent international studies have suggested that some of these newly found, very small thyroid cancers (known as micro-papillary thyroid cancers) may not need to be treated right away but instead can be safely watched. Ongoing clinical trials in the US are now looking at this same approach.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as editors and translators with extensive experience in medical writing.

Bible KC, Suman VJ, Molina JR, et al. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: Results of a phase 2 consortium study. Lancet Oncol . 2010;11:962−972.

Carr LL, Mankoff DA, Goulart BH, et al. Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res . 2010;16:5260−5268.

Cohen E, Rosen L, Vokes E et al. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: Results from a phase II study. J Clin Oncol . 2008;26:4708−4713.

Fagin JA. Challenging dogma in thyroid cancer molecular genetics — role of RET/PTC and BRAF in tumor initiation. J Clin Endocrinol Metab . 2004;89:4280−4284.

Gupta-Abramson V, Troxel A, Nellore A, et al. Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol . 2008:26:4714−4719.

Ho AL, Grewal RK, Leboeuf R, et al. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med . 2013 Feb 14;368(7):623-32.

Kloos RT, Ringel MD, Knopp MV, et al. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol . 2009;27:1675−1684.

Savvides P, Nagaiah G, Lavertu P, Fu P, Wright JJ, Chapman R, Wasman J, Dowlati A, Remick SC. Phase II trial of sorafenib in patients with advanced anaplastic carcinoma of the thyroid. Thyroid . 2013 May;23(5):600-4. Epub 2013 Apr 18.

Schneider TC, Abdulrahman RM, Corssmit EP, Morreau H, Smit JW, Kapiteijn E. Long-term analysis of the efficacy and tolerability of sorafenib in advanced radio-iodine refractory differentiated thyroid carcinoma: final results of a phase II trial. Eur J Endocrinol . 2012 Nov;167(5):643-50. Epub 2012 Aug 23.

Smallridge RC, Copland JA, Brose MS, et al. Efatutazone, an oral PPAR-γ agonist, in combination with paclitaxel in anaplastic thyroid cancer: results of a multicenter phase 1 trial. J Clin Endocrinol Metab . 2013 Jun;98(6):2392-400. Epub 2013 Apr 15.

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Why rates of cancer among Millennials and Gen X are on the rise in America

William Brangham William Brangham

Sam Lane Sam Lane

Maea Lenei Buhre Maea Lenei Buhre

Kaisha Young Kaisha Young

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• Copy URL https://www.pbs.org/newshour/show/why-rates-of-cancer-among-millennials-and-gen-x-are-on-the-rise-in-america

While cancer deaths in the U.S. have decreased in recent years, experts say one group has seen an overall rise in cancer rates: younger Americans. William Brangham spoke with Karen Knudsen, CEO of the American Cancer Society, to learn more about the shift in demographics and what can be done to address it.

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Notice: Transcripts are machine and human generated and lightly edited for accuracy. They may contain errors.

Stephanie Sy:

While cancer deaths in the US have decreased in recent years, experts say one age group has seen an overall rise in cancer rates younger Americans. William Brangham has the latest on the shifting demographics and what can be done to address it.

William Brangham:

They're called early onset cancers, which means cancer among adults under 50, and they are on the rise. A groundbreaking report from the American Cancer Society looked at rates of 34 different kinds of cancer over several decades and found that 17 of them were more prevalent in millennials and Gen Xers. So what is going on here?

Doctor Karen Knudsen is the CEO of the American Cancer Society. Doctor Knudsen, thank you so much for being here. I think the findings in this caught a lot of people by surprise. When you look at the overall study, what stands out most to you?

Dr. Karen Knudsen, CEO, American Cancer Society:

Well, you know, there are some surprises here, but in fact, we've been seeing some early indicators about this rise in cancers at an earlier age over the last several years, early onset colorectal cancer, I think, was the canary in the coal mine here, where we saw declining incidents in populations in the 65 and above, but rising in those that are 50 and younger. These are ages for which we previously not thought about someone being at risk for colorectal cancer.

So clearly, something is changing, and this new study highlights that with 50 percent as you said, of the studies that of the cancers that we looked at on the rise in Gen xers and Millennials as compared to Baby Boomers.

Do we know why this is happening? Because, again, the traditional I'm no oncologist, but the traditional understanding is older people tend to get more cancers. You get cancer as you get older. Why is this happening with younger people?

Karen Knudsen:

So what that is true, not for all, but for most cancers, age is a risk factor. So that is without question, true. But when we look at these cancer rates, they are sometimes two to three times higher in incidence for the Gen X and Millennial population as compared to Baby Boomers.

So we look at those data, we think that the typical risks are still at play. Obesity. 10 of those 17 cancers are linked to obesity. Lifestyle. So sedentary lifestyle, of course, increases cancer risk alongside an unhealthy diet, lack of fruits, vegetables, grain fiber, et cetera.

So we know that those typical cancer risks are at play. But there must be something else, because these rates are so different as compared to the previous generation, the baby boomers.

One of the things we also are concerned about is, if you get cancer, whether or not it ends up ending your life. What do we know about cancer death rates?

That's right. So when we actually looked in these three different age populations, we could follow cancer mortality as well in a subset of them, and we saw five actually that were of increased mortality rates in Gen X and Millennial populations. It was liver cancer, specifically for women, uterine cancer, gallbladder cancer, testicular cancer, which is not a cancer of aging, and colorectal cancer, which we talked about.

So these leave then open questions for which more cancer research will be needed in order to address and we can speculate as to what are some of these additional exposures that someone may have been subject two, or could it be a compendium of exposures, diet and lifestyle?

What I would say is that what we know right now is of all the cancers that we track every year, our own research estimates that up to 40 percent of them are preventable due to behavior modification, things like having that healthy diet, staying active, maintaining a healthy body weight. Of course, don't smoke, limit alcohol and get screened.

So we know that early detection saves lives, and that increase, that increased survivorship is, of course, something that is well within means for screenable cancers.

On that issue of screening, given what this study reflects, do you think we ought to be changing the guidance that we give to not just to doctors, but to individuals, as far as when you get checked? How often you get checked?

Such an important question. So it's important to remember that screening is not just about your age, that's one portion, but it's also about your genetics, if you know it, your family history, your own medical history, and your risk of exposures.

So never too early to when you are at your physician, ask and take ownership of it on your own. What is the right screening plan for me, so that all of those different criteria can be taken into account.

Now, as relates to cancer screening guidelines, we of course, look at this regularly. We are in the process right now of rewriting our prostate cancer screening guideline, but we were the first at the American Cancer Society to drop first colonoscopy from age 50 for people of average risk to age 45 because of these trends of early onset.

So we will continue to monitor and determine whether or not the screening guidelines require additional modification the science will lead us.

Do you think younger people are getting the news about this? Do you feel like that this message is percolating out into society?

I think that they are and hearing reports like this can help them take agency over their own health, those prevention behaviors. We talked about how this discussion about screening, but also don't ignore symptoms. So if you're 44 years old and you're experiencing something that seems like it could be associated with colorectal cancer risk. Don't wait. Be seen and have that discussion with your physician, even if you're too young to technically have had your first colonoscopy. Don't ignore symptoms.

But it's also important to note that on balance, there's good news as well for cancers overall since 1991 which was the high water mark for cancer in this country, we have reduced the overall cancer mortality rate by 33 percent so there is more hope than ever before, which is altogether more reason to not ignore symptoms, take agency over your own health, for prevention, but also having symptoms addressed.

Like that there's at least a little bit of good news in that. Doctor Karen Knudsen, CEO of the American Cancer Society, thank you so much for joining us.

My pleasure. Thank you for having me.

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How to Find the Right Oncologist for You

After a cancer diagnosis, it’s one of the most important decisions you’ll make.

By Ted Alcorn

After a career as a golf professional in southeastern New Mexico, Doug Lyle, 76, decided he had somewhere better to be than on the course: spending time with his new grandchild. Then this summer, just as he was settling into retirement, he learned he had prostate cancer.

“When you’re first diagnosed, you immediately go to the internet, and you can be overwhelmed in short order,” he said. “The more you read about it, the more complicated it gets.”

One of the first and most important choices he had to make was who his oncologist would be. Many of the two million patients diagnosed with cancer in the United States each year get the news from a primary care doctor. Those patients might accept a referral to an oncologist without question. But research suggests that it’s worth considering the choice closely: It can shape the care you receive , your satisfaction with the treatment and your chances of survival .

Scour the information available.

Not everyone has a choice of oncologists. There are fewer providers in rural areas, and patients must travel farther to reach them. Insurers may only cover certain clinicians and hospitals. And patients from certain populations have less access to oncologists for a range of reasons, which may affect the care they receive. For example, research suggests that Black and Hispanic women with breast cancer are more likely than white women to experience delays in starting radiotherapy. And Black men with prostate cancer are less likely than white men to receive treatment that’s intended to cure their condition, even when they’re at similar stages of disease.

No matter your circumstances, you should feel empowered to have a say in who treats your cancer.

Ideally, experts said, you’d be able to easily compare doctors’ levels of experience and the outcomes of patients they’ve treated with your same diagnosis. But such apples-to-apples comparisons are not always easy to make. But “right now, there are no publicly available data to help a patient with cancer say, ‘Oh, this is where I want to go,’” said Dr. Nancy Keating, a physician and professor of health care policy and medicine at Harvard Medical School. (And even if there were, apples-to-apples comparisons are not always easy to make, since patient populations vary from one doctor to the next).

Still, there are some accreditations to look for. The National Cancer Institute has given a special designation to 72 cancer centers , which must show they treat patients in accordance with the latest evidence and also conduct research into new therapies. The American College of Surgeons Commission on Cancer has accredited over 1,500 programs that meet certain standards. And the American Society of Clinical Oncology has several certification programs, including a list of 300 practices recognized for their quality and safety.

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Advances in Prostate Cancer Research

Nanoparticles are tested as a means to deliver drugs to prostate cancer cells.

NCI-funded researchers are working to advance our understanding of how to prevent, detect, and treat prostate cancer.  Most men diagnosed with prostate cancer will live a long time, but challenges remain in choosing the best treatments for individuals at all stages of the disease.

This page highlights some of the latest research in prostate cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Studying Early Detection for Men at High Risk

Men with certain inherited genetic traits are at increased risk for developing prostate cancer. Examples of such traits include inherited BRCA gene mutations and Lynch syndrome . No clear guidelines exist for when or how—or if—to screen men at high genetic risk for prostate cancer. 

NCI researchers are using magnetic resonance imaging (MRI) of the prostate in men at high risk of developing prostate cancer to learn more about how often and how early these cancers occur. They’re also testing whether regular scans in such men can detect cancers early, before they spread elsewhere in the body ( metastasize ).

Diagnosing Prostate Cancer

Improving biopsies for prostate cancer.

Traditionally, prostate cancer has been diagnosed using needles inserted into the prostate gland in several places under the guidance of transrectal ultrasound (TRUS) imaging to collect samples of tissue. This approach is called systematic biopsy .

However, ultrasound does not generally show the location of cancer within the prostate. It is mainly used to make sure the biopsy needles go into the gland safely. Therefore, biopsy samples using ultrasound guidance can miss cancer altogether. Or they may identify low-grade cancer while missing areas of high-grade , potentially more aggressive cancer, particularly in Black men.

Some doctors, concerned that a systematic biopsy showing only low-grade cancer could have missed a high-grade cancer, may suggest surgery or radiation. However, in some cases these treatments will be for a cancer that may have never caused a problem, which is considered overtreatment .

Using MRI and ultrasound . Scientists at NCI have developed a procedure that combines magnetic resonance imaging (MRI) with TRUS for more accurate prostate biopsies. MRI can locate potential areas of cancer within the gland but is not practical for real-time imaging to guide a prostate biopsy. The procedure, known as MRI-targeted biopsy, uses computers to fuse an MRI image with an ultrasound image. This lets doctors use ultrasound guidance to take biopsy samples of areas of possible cancer seen on MRI.

NCI researchers have found that combining MRI-targeted biopsy with systematic biopsy can increase the detection of high-grade prostate cancers while decreasing detection of low-grade cancers that are unlikely to progress. 

Testing machine learning . Researchers are testing the use of machine learning , also called artificial intelligence (AI), to better recognize suspicious areas in a prostate MRI that should be biopsied. AI is also being developed to help pathologist s who aren't prostate cancer experts accurately assess prostate cancer grade . Cancer grade is the most important factor in determining the need for treatment versus  active surveillance .

Finding small amounts of prostate cancer using imaging and PSMA

NCI-supported researchers are developing new imaging techniques to improve the diagnosis of recurrent prostate cancer. A protein called prostate-specific membrane antigen (PSMA) is found in large amounts—and almost exclusively—on both cancerous and noncancerous prostate cells. By fusing a molecule that binds to PSMA to a compound used in PET  imaging, scientists have been able to see tiny deposits of prostate cancer that are too small to be detected by regular imaging.

The Food and Drug Administration (FDA) has approved two such compounds for use in PSMA-PET imaging of men with prostate cancer. These approvals are for men whose cancer may have spread to other parts of the body but is still considered curable, either with surgery or other treatments.

The ability to detect very small amounts of metastatic prostate cancer could help doctors and patients make better-informed treatment decisions. For example, if metastatic cancer is found when a man is first diagnosed, he may choose an alternative treatment to surgery because the cancer has already spread. Or doctors may be able to treat cancer recurrence—either in the prostate or metastatic disease—earlier, which may lead to better survival. Studies are being done to determine if such early detection can improve outcomes.

As part of the Cancer Moonshot℠ , NCI researchers are testing whether PSMA-PET imaging can also identify men who are at high risk of their cancer recurring. Such imaging may eventually be able to help predict who needs more aggressive treatment—such as radiation therapy in addition to surgery—after diagnosis.

Research teams are also looking at:

• whether certain patterns seen on PSMA-PET tests taken over time may indicate an increased risk of recurrence after initial treatment
• how small metastases discovered with PSMA change over time , with or without treatment

New Prostate Cancer Treatments

Standard treatments for prostate cancer that has not spread elsewhere in the body are surgery or radiation therapy, with or without hormone therapy . 

Active surveillance is also an option for men who have a low risk of their cancer spreading. This means monitoring the cancer with regular biopsies and other tests, and holding off on treatment unless there is evidence of progression. Rates of active surveillance more than doubled between 2014 and 2021 , to almost 60% of US men diagnosed with low-risk prostate cancer. 

Hormone therapy for prostate cancer

Over the last decade, several new approaches to hormone therapy for advanced or metastatic prostate cancer have been approved for clinical use.

Many prostate cancers that originally respond to treatment with standard hormone therapy become resistant over time, resulting in castrate-resistant prostate cancer  (CRPC). Four newer drugs have been shown to extend survival in some groups of men with CRPC. All inhibit the action of hormones that drive CRPC:

• enzalutamide (Xtandi) 
• abiraterone (Zytiga)
• darolutamide (Nubeqa)
• apalutamide (Erleada)

These drugs are now also used in some people whose prostate cancer still responds to standard hormone therapies but has spread elsewhere in the body (metastasized).

Scientists are continuing to study novel treatments and drugs, along with new combinations of existing treatments, in men with metastatic and castrate-resistant prostate cancer.

Hormone therapy for biochemically recurrent prostate cancer

A biochemical recurrence is a rise in the blood level of PSA in people with prostate cancer after treatment with surgery or radiation. In 2023, the FDA approved enzalutamide, given alone or with another drug called leuprolide, for some men who have a biochemical recurrence and are at high risk of their cancer spreading but don’t have signs on regular imaging that their cancer has come back.

Use of this drug combination can improve how long these men live without their cancer spreading. But it’s not yet known if using the drugs in this manner improves how long people live overall. Researchers are trying to determine which patients will benefit most from these types of treatments.

PARP inhibitors for prostate cancer

A PARP inhibitor is a substance that blocks an enzyme in cells called PARP. PARP helps repair DNA when it becomes damaged. Some prostate tumors have genetic changes that limit their ability to repair DNA damage. These tumors may be sensitive to treatment with PARP inhibitors. Some people also inherit genetic factors that limit their body’s ability to repair DNA damage. Prostate tumors in such people can also be treated with PARP inhibitors.  

Two PARP inhibitors, olaparib (Lynparza) and rucaparib (Rubraca) , have been approved for use alone in some men whose prostate cancer has such genetic changes and has metastasized , and whose disease has stopped responding to standard hormone treatments alone.

Ongoing studies are looking at combining PARP inhibitors with hormone therapies. Since 2023, the FDA has approved three such combinations for some men with metastatic prostate cancer:

• the hormone therapy enzalutamide (Xtandi) with the PARP inhibitor, talazoparib (Talzenna)
• the hormone therapy abiraterone (Zytiga) with the PARP inhibitor olaparib (Lynparza)
• the hormone therapy abiraterone with the PARP inhibitor niraparib (Akeega)

Immunotherapy: vaccines for prostate cancer

Immunotherapies are treatments that harness the power of the immune system to fight cancer. These treatments can either help the immune system attack the cancer directly or stimulate the immune system in a more general way.

Vaccines and checkpoint inhibitors are two types of immunotherapy being tested in prostate cancer. Treatment vaccines are injections that stimulate the immune system to recognize and attack a tumor.

One type of treatment vaccine called sipuleucel-T (Provenge) is approved for men with few or no symptoms from metastatic CRPC.

Immunotherapy: checkpoint inhibitors for prostate cancer

An immune checkpoint inhibitor is a type of drug that blocks proteins on immune cells, making the immune system more effective at killing cancer cells.

Two checkpoint inhibitors,  pembrolizumab (Keytruda)  and dostarlimab (Jemperli) have been approved for the treatment of tumors, including prostate cancers, that have specific genetic features . Pembrolizumab has also been approved for any tumor that has metastasized and has a high number of genetic mutations .

But relatively few prostate cancers have these features, and prostate cancer in general has largely been resistant to treatment with checkpoint inhibitors and other immunotherapies, such as CAR T-cell therapy .

Research is ongoing to find ways to help the immune system recognize prostate tumors and help immune cells penetrate prostate tumor tissue. Studies are looking at whether combinations of immunotherapy drugs, or immunotherapy drugs given with other types of treatment, may be more effective in treating prostate cancer than single immunotherapies alone.

PSMA-targeted radiation therapy

Scientists have developed targeted therapies based on PSMA, the same protein that is used for imaging prostate cancer. For treatment, the molecule that targets PSMA is chemically linked to a radioactive  substance. This new compound can potentially find, bind to, and kill prostate cancer cells throughout the body.

In a recent clinical trial, men with a type of advanced prostate cancer who received a PSMA-targeting drug lived longer than those who received standard therapies . This trial led to FDA approval of the drug,  Lu177-PSMA-617 (Pluvicto) , to treat some people with metastatic prostate cancer who had previously received chemotherapy. 

An ongoing study is testing the use of Lu177-PSMA-617 in some people with metastatic prostate cancer who haven't yet received chemotherapy. Other clinical trials are testing PSMA-targeting drugs in patients with earlier stages of prostate cancer, and in combination with other treatments, including targeted therapies like PARP inhibitors and immunotherapy.

Personalized clinical trials for prostate cancer

Research is uncovering more information about the genetic changes that happen as prostate cancers develop and progress. Although early-stage prostate cancer has relatively few genetic changes compared with other types of cancer, researchers have learned that metastatic prostate cancers usually accumulate more changes as they spread through the body.

These changes may make men with metastatic prostate cancers candidates for what are called “basket” clinical trials of new drugs. Such trials enroll participants based on the changes found in their cancer, not where in the body the cancer arose. In the NCI-MATCH trial , a high percentage of enrolled men with advanced prostate cancer had genetic changes that could potentially be targeted with investigational drugs.

NCI-Supported Research Programs

Many NCI-funded researchers working at the National Institutes of Health campus, as well as across the United States and world, are seeking ways to address prostate cancer more effectively. Some of this research is basic, exploring questions as diverse as the biological underpinnings of cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate basic information into improving patient outcomes. The programs listed below are a small sampling of NCI’s research efforts in prostate cancer.

• The Cancer Biomarkers Research Group promotes research on cancer biomarkers and manages the Early Detection Research Network (EDRN) . EDRN is a network of NCI-funded institutions that are collaborating to discover and validate early detection biomarkers.
• Within the  Center for Cancer Research , the Prostate Cancer Multidisciplinary Clinic (PCMC) provides comprehensive consultations on diagnosis and treatment options to people with newly-diagnosed prostate cancer. 
• The Prostate Specialized Programs of Research Excellence (Prostate SPOREs) are designed to quickly move basic scientific findings into clinical settings. The Prostate SPOREs support the development of new therapies and technologies and studies to better understand how to prevent, monitor, and treat prostate cancer.
• The NCI Cancer Intervention and Surveillance Modeling Network (CISNET)  focuses on using modeling to improve our understanding of which men are most likely to benefit from PSA-based screening. CISNET also studies treatment strategies for prostate cancer and approaches for reducing prostate cancer disparities.
• The NCI Genitourinary Malignancies Center of Excellence (GUM-COE) brings together scientists studying genitourinary cancers (GU) from across NCI’s Center for Cancer Research and the Division of Cancer Epidemiology and Genetics, as well as investigators who study GU malignancies in other institutes of NIH. The goal is to provide a centralized resource and infrastructure to accelerate the discovery, development, and delivery of interventions for the prevention, diagnosis, and treatment of these cancers.
• The Research on Prostate Cancer in Men with African Ancestry (RESPOND) study is the largest-ever coordinated research effort to study biological and non-biological factors associated with aggressive prostate cancer in African American men. The study , launched by NCI and the National Institute on Minority Health and Health Disparities in partnership with the Prostate Cancer Foundation, is looking at the environmental and genetic factors related to the aggressiveness of prostate cancer in African American men to better understand why they disproportionally experience aggressive disease.

Clinical Trials

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for prostate cancer  prevention , screening , and treatment .

Prostate Cancer Research Results

The following are some of our latest news articles on prostate cancer research:

• Enzalutamide Gets Added Approval for Prostate Cancer That Hasn’t Spread
• FDA Approves New Initial Treatment Option for Some Metastatic Prostate Cancers
• Is a Genomic Test Better at Finding Aggressive Prostate Cancer?
• Active Surveillance for Low-Risk Prostate Cancer Continues to Rise
• Darolutamide Extends Survival for Some People with Metastatic Prostate Cancer
• Shorter, More Intensive Radiation Safe after Surgery for Prostate Cancer

View the full list of Prostate Cancer Research Results and Study Updates .