ROCHESTER, Minn. — Mayo Clinic researchers have identified a strategy that could help chimeric antigen receptor-T cell therapy, or CAR-T cell therapy, overcome a major barrier to treating solid tumors: Cancer cells can change in ways that allow them to hide from immune cells designed to attack them.

In a preclinical study published in Molecular Cancer, researchers found that drugs used to treat advanced thyroid cancer can restore a marker on aggressive thyroid cancer cells, making the cancer visible again to specially engineered CAR-T cells. Combining the drugs with CAR-T cell therapy resulted in better tumor control and survival in preclinical models than either approach alone.

Rather than further modifying CAR-T cells to recognize cancers that have lost their targets, researchers sought to change the tumor so the target reappears.

"We often think about engineering the immune cell to overcome resistance," says co-senior author Saad Kenderian, M.B., Ch.B., a hematologist and oncologist at Mayo Clinic in Minnesota. "This work shows another possibility."

Making an aggressive cancer visible again

CAR-T cell therapy engineers T cells — immune cells that help protect the body from disease — to recognize a specific target, or antigen, on cancer cells. The approach has transformed treatment for some blood cancers but has been less successful against solid tumors.

One reason is that solid tumors can lose or reduce the antigens CAR-T cells are designed to recognize, making it more difficult for the engineered cells to identify and destroy the cancer.

The Mayo Clinic team focused on the thyroid-stimulating hormone receptor (TSHR), a protein found primarily on thyroid cells. CAR-T cells targeting this receptor showed strong antitumor activity against thyroid cancers with high TSHR levels. Their effectiveness was more limited against anaplastic thyroid cancer, the most aggressive form of the disease with low or no TSHR expression.

Turning the target back on

Researchers investigated whether they could restore TSHR through a process known as redifferentiation, in which aggressive cancer cells regain some of the biological features they had lost.

They used drugs that inhibit the mitogen activated protein kinase (MAPK) signaling pathway, including trametinib and dabrafenib, which are approved to treat advanced thyroid cancer.

In patient-derived models of anaplastic thyroid cancer, MAPK inhibition increased TSHR expression on tumor cells. When researchers combined the drugs with TSHR-targeted CAR-T cells, the combination produced stronger tumor control and survival than either treatment alone.

"One of the key discoveries from our work is that antigen density matters. We showed that restoring TSHR expression with combination therapy can sensitize aggressive thyroid tumors to CAR-T cell attack, effectively turning a suboptimal target into a more vulnerable one. This approach may provide a new framework for enhancing CAR-T therapies across solid tumors where target expression is limited," says co-first author Claudia Manriquez Roman, Ph.D., process development engineer at Mayo Clinic in Minnesota.

Researchers also found that the MAPK inhibitors did not appear to interfere with the CAR-T cells' ability to multiply or attack cancer cells. Instead, the drugs created a temporary window in which  the CAR-T cells could target cancer cells that had previously escaped detection.

TSHR expression declined after MAPK inhibitor treatment stopped, but two weeks of concurrent treatment was sufficient to improve CAR-T cell activity in the preclinical models.

"What’s exciting about this approach is that we're taking advantage of the cancer cell's own biology to restore TSHR expression by blocking MAPK signaling with molecular targeted drugs," says co-senior author John Copland III, Ph.D., cancer biologist and translational researcher at Mayo Clinic in Florida. Dr. Copland noted that approximately 2,500 Americans die per year from metastatic thyroid cancer disease. 

A potential strategy beyond thyroid cancer

Although the study focused on thyroid cancer, the concept could have implications for other solid tumors where treatments use immune therapy that targets similar surface markers.

Researchers are completing studies needed to support phase 1 clinical trial testing of TSHR-targeted CAR-T cells. The therapy could be studied alone in patients whose tumors continue to express TSHR or in combination with MAPK inhibitors in patients whose tumors have lost TSHR expression.

The researchers hope the approach ultimately could lead to another treatment option for patients with cancers that no longer respond to available therapies.  

For a complete list of authors, disclosures and funding, read the study.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post Study shows reprogramming thyroid tumors may improve CAR-T cell therapy appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have found that artificial intelligence (AI)-enabled spatial analysis can identify patterns in routine pathology slides that may help clinicians identify which patients with pancreatic cancer are at greater risk of recurrence after treatment and surgery.

The study, published in Clinical Cancer Research, suggests that looking at how residual cancer is organized — not just how much remains — could eventually improve estimates of recurrence risk, particularly for patients whose tumors show only a limited response to chemotherapy before surgery.

Patients with a more fragmented, intermixed pattern of cancer and the surrounding tissue, or stroma, had earlier recurrence. The amount of residual cancer alone did not reliably separate patients at higher and lower risk.

"Current pathology assessments largely tell us how much tumor is left after treatment. We wanted to know whether the geography of that remaining cancer could reveal additional biology about recurrence risk," says Ryan Carr, M.D., Ph.D., a Mayo Clinic oncologist and senior author of the study.

Dr. Carr and his team used an AI tool to identify cancer and stromal regions on standard pathology slides, then measured how those regions formed patches, boundaries and mixed areas to evaluate spatial patterns tied to a higher risk of recurrence. 

Reading the geography of cancer 

The study analyzed tissue from 203 patients with pancreatic ductal adenocarcinoma who received treatment before surgery but showed only a limited pathologic response. The researchers combined an AI-enabled digital pathology platform with methods adapted from landscape ecology to analyze standard hematoxylin and eosin, or H&E, slides. The approach measured tissue shape, fragmentation, and the degree to which the cancer and stroma were intermixed.

The work builds on Dr. Carr's broader research applying ecological principles to cancer. His team uses machine learning and spatial analysis to map the pancreatic cancer ecosystem and study how cancer cells interact with neighboring cells and tissues — relationships that may influence treatment resistance and recurrence.

Two spatial signatures predicted disease-free survival even after accounting for stage, lymph node status, and other established clinical and pathologic risk factors.

In one model, high-risk patients had a 71% higher adjusted risk of recurrence. In another, high-risk patients had more than twice the adjusted risk. These spatial models helped distinguish patients at higher and lower risk when standard measures, including how much cancer remained, did not.

Because the approach uses pathology slides already generated as part of routine care, it could potentially give clinicians additional information to inform recurrence risk without requiring another tissue test.

Linking tumor patterns and immune response 

"What is exciting is that this information is already present in the tissue," Dr. Carr says. "AI-enabled analysis gives us a way to measure features that are difficult to capture by eye and potentially add another layer of precision to how we assess risk after surgery."

The research also found that high-risk spatial patterns contained fewer immune cells within the cancer itself, with immune cells tending to collect around the tumor instead of entering it. The finding underscores the importance of the tumor microenvironment — the cells and tissues surrounding a tumor — in treatment resistance and disease behavior.

More broadly, the work aligns with Mayo Clinic's Precure Research priority to use data and technology to predict risk earlier and create opportunities to intercept serious disease before it advances.

"Our long-term goal is to better identify which patients remain at greatest risk and ultimately use that knowledge to guide more individualized surveillance, adjuvant therapy and clinical trial design," Dr. Carr says.

The researchers say the results are promising but need to be confirmed in prospective studies before this approach could be used to inform clinical decision-making.

The research was supported in part by the Gerstner Family Career Development Award, the Grand Forks Career Development Award, the Mayo Clinic Center for Clinical and Translational Science, and the ARPA-H ADAPT program. For a complete list of authors, disclosures and funding, review the study. 

### 

About Mayo Clinic 
Mayo Clinic  is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

Media contact: 

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu 

The post AI-enabled analysis of pathology slides may help assess risk of pancreatic cancer recurrence    appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Three new articles from The Lancet Hematology published today examine how clinicians and researchers can better identify, track and measure the effects of blood cancer treatments on patients during treatment and over the long term.

Gita Thanarajasingam, M.D., a Mayo Clinic hematologist and oncologist, leads The Lancet Haematology's Adverse Events Reporting Series. The Series focuses on how clinicians care for people after treatment, how they measure treatment side effects and whether digital tools can help detect and manage those effects in real-world practice.

"Blood cancer treatments continue to become more effective and patients are living longer," says Dr. Thanarajasingam. "Just as we continue to evolve our treatments and detection in cancer, however, we need to evolve how we measure the effects on patients and their lives."

First launched in 2018, the Commission explores how newer treatments can be evaluated and whether new questions and tools can improve assessment. Current models for measuring treatment side effects may not adequately or consistently capture the duration and impact of symptoms on patients' lives. For example, a grading system might rank six months of mild nausea lower than four days of severe nausea without fully accounting for how a persistent symptom affects a patient's daily life.

The articles also examine the need for longer-term assessment. Many treatment studies measure outcomes only through five years after treatment, potentially leaving gaps in identifying and addressing health problems that emerge later. The reports suggest that cancer care should extend beyond treatment and that new approaches could help support patients’ health and quality of life during and after treatment.

The articles also describe how technology could support changes in how treatment effects are measured. Digital tools such as symptom-reporting apps, wearable devices and artificial intelligence could shift cancer safety monitoring from periodic assessments of what has already happened toward more continuous monitoring.

"Technology can enable new standards in care simply because it could offer more and real-time data," says Dr. Thanarajasingam. The report cautions, however, that new technologies are only a valuable catalyst if they are accurate, useful, equitable and built around patients.

"Complete cancer care is driven by the patient and their needs. For every therapeutic advance we make, we must also evolve our assessment standards and take advantage of new information to keep people's full and ideally, long lives at the core of our decision-making," says Dr. Thanarajasingam. "Just as we are now able to better personalize treatments, so, too, should we begin to address the whole person and their long-term needs."

For a complete list of commission members, disclosures and funding, review the articles in The Lancet Haematology.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic researcher leads Lancet commission reports on life during and after blood cancer treatment appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have estimated the risk that pancreatic cysts with worrisome or high-risk features will progress to pancreatic cancer or advanced precancerous changes within three years. The findings, published in Gastroenterology, could help physicians and patients better assess risk and make more informed decisions about whether to monitor a cyst or consider surgery. 

The prospective study found that risk increased with the number of worrisome features, or findings that the cyst needs closer monitoring. Patients whose cysts had one worrisome feature had about a 2% chance of developing pancreatic cancer or advanced precancerous changes within three years. The risk rose to 4% for those with two worrisome features and 18% for those with three or more. 

"This information will help us counsel patients. If we want to intercept pancreatic cancer while also sparing patients from unnecessary interventions, we must really know what is likely to become cancer and what is not," says Shounak Majumder, M.D., lead author and a gastroenterologist at Mayo Clinic.  

What does pancreatic cyst risk mean for patients?  

Pancreatic cysts are common and often discovered during imaging for an unrelated reason. Most do not become cancerous, but certain features seen on imaging can indicate a greater risk. Pancreatic cysts are classified as having high-risk features, worrisome features or neither. 

Pancreatic cysts without worrisome or high-risk features have a relatively low likelihood of progression to cancer. Cysts with high-risk features may prompt physicians to recommend surgery because of greater concern about cancer or advanced precancerous changes. Cysts with worrisome features often are monitored closely, although some may also require surgery.  

"Sometimes, we are unable to reliably determine whether a cyst will become pancreatic cancer or not," Dr. Majumder says. "That uncertainty creates a lot of anxiety for some patients undergoing surveillance, and some will opt for surgery." 

More precise estimates of progression risk can help patients and physicians weigh the potential benefits of surveillance and surgery.   

How did researchers determine pancreatic cancer risk?  

The study followed 230 people with pancreatic cysts that had worrisome or high-risk features. Unlike studies that look back at existing medical records or primarily include patients who underwent surgery, researchers enrolled participants and followed them over time, regardless of whether they chose surgery or surveillance. 

Of the 230 participants, 32 underwent surgery within the first three months after enrollment, and 198 entered clinical surveillance. Among those monitored, 185 had cysts with worrisome features, and 13 had cysts with high-risk features.  

The study found that patients with multiple worrisome features may represent a substantially higher-risk subgroup, while risk was not markedly elevated in patients with a single worrisome feature. 

Pancreatic cancers diagnosed among patients under careful surveillance were detected at a very early stage, suggesting that surveillance of appropriately risk-stratified patients may provide an opportunity to catch pancreatic cancer early. The finding suggests that regular surveillance may be an appropriate approach for some patients rather than immediate surgery. 

The three-year risk estimates also provide a benchmark for evaluating blood tests and designing studies of other approaches to early pancreatic cancer detection. 

Can blood tests and biomarkers predict pancreatic cancer risk? 

In a separate study led by Dr. Majumder and colleagues published in Clinical Gastroenterology and Hepatology, researchers examined CA 19-9, a blood biomarker that may be elevated in people with pancreatic cancer and is sometimes used to monitor pancreatic cysts. 

An elevated CA 19-9 result alone did not reliably predict which patients with pancreatic cysts would develop cancer. Among patients with low-risk cysts who had an elevated CA 19-9 level, none developed pancreatic cancer during the study's follow-up period. 

The findings suggest that a blood biomarker test should be considered with other information about a patient's health and cancer risk. They also underscore the need for new biomarker tests that can reliably detect the earliest stages of cancer in patients with pancreatic cysts. 

The data from these studies could help researchers design larger studies and clinical trials of new approaches to the early detection and prevention of pancreatic cancer as part of a broader effort at Mayo Clinic known as the Precure Research initiative.  

"The goal is more precise, personalized surveillance and an early detection approach that identifies patients who may benefit from earlier intervention while helping those at lower risk avoid unnecessary procedures and major surgery," says Dr. Majumder.  

For a complete list of authors, disclosures and funding, review the study.  

### 

About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact:  

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu  

The post Mayo Clinic study estimates cancer risk in patients with pancreatic cysts, advancing early detection  appeared first on Mayo Clinic News Network.

JACKSONVILLE, Fla. — Mayo Clinic researchers have developed an experimental drug with the help of artificial intelligence (AI) to target the "undruggable" PDZ-domain of GIPC1 protein that helps different types of cancer, including pancreatic cancer, to grow and resist treatment. In laboratory studies, the drug slowed tumor growth, improved survival and enhanced the effects of the chemotherapy drug gemcitabine.

The findings, published in Cell Reports, also demonstrate how AI could help develop a small molecule inhibitor of a target protein that can be less toxic and speed the discovery of new cancer treatments.

Pancreatic cancer is one of the most difficult cancers to treat because it is often diagnosed after it has spread and is resistant to many current therapies. While survival rates remain low, advances in research are creating new opportunities to develop more effective treatments. This study represents one of those promising advances, offering a potential new strategy for targeting pancreatic cancer.

Using AI, in collaboration with Sravathi AI Technology for IP Sharing, a company based in Bangalore, India, the research team screened nearly 40,000 potential compounds before identifying one that blocks GIPC1. The experimental drug also showed early signs of changing the environment around tumors in ways that could improve future combination therapies. Additional studies are needed before it can be tested in people.

"Pancreatic cancer has remained exceptionally difficult to treat because tumors rapidly adapt and become resistant to many available therapies," says Debabrata (Dev) Mukhopadhyay, Ph.D., senior author of the study and a cancer researcher at Mayo Clinic in Florida. "Our study demonstrates that AI can help us identify entirely new therapeutic opportunities against targets that have historically been considered undruggable. While these findings are preclinical, they provide a strong foundation for the next phase of research."

The therapy remains experimental, and additional studies are needed to evaluate its safety and determine whether it can advance to clinical trials.

This research was supported in part by the National Institutes of Health, the Florida State Fund for the Casey DeSantis Cancer Research Program and the U.S. Department of Defense. For a complete list of authors, disclosures and funding, review the study.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post First-in-class small molecule inhibitor designed with AI support shows promise against pancreatic cancer in preclinical studies appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have identified a protein that cancer cells use to shut down the body's immune response, a discovery that could help scientists develop new treatments that make cancer immunotherapies more effective.

Published in the Journal of Clinical Investigation, the study identifies a previously unknown role for a protein called TRAILshort, which acts like an immune "off switch." The researchers found that TRAILshort prevents T cells — the immune system's primary cancer-fighting cells — from recognizing and destroying cancer and virus-infected cells. In preclinical models, blocking the protein restored T-cell activity and improved immune response. 

The researchers also found that TRAILshort reduces the effectiveness of chimeric antigen receptor-T cell therapy (CAR-T cell therapy), one of the most advanced forms of cancer immunotherapy. Their findings suggest that therapies designed to block TRAILshort could improve CAR-T treatment and potentially benefit other immune-based cancer therapies.

"What strikes me most is that TRAILshort appears in cancer, HIV, COVID-19, tuberculosis, lupus and Crohn's disease — almost every condition where the immune system is failing or misfiring. That tells us we may have identified a fundamental switch in human immunity, not just a curiosity in one disease," says Andrew Badley, M.D., senior author of the study. Dr. Badley is the HH Sheikh Khalifa Bin Zayed Al Nahyan Professor of Infectious Diseases and an immunologist at Mayo Clinic.

How cancer disrupts the immune response 

Mayo Clinic researchers first discovered TRAILshort while studying HIV nearly 15 years ago. In 2020, they found that cancer cells also produce the protein, but how it suppressed T-cell activity remained unknown. This new study reveals the mechanism for the first time.

Researchers found elevated levels of TRAILshort in melanoma, lung, breast, pancreatic and ovarian cancers, as well as Hodgkin lymphoma. Elevated levels also were found in infectious diseases, including COVID-19, tuberculosis and hepatitis C.

Using highly specific antibodies and engineered preclinical models, the team found that TRAILshort activates SHP-1, a protein that acts as a molecular brake, shutting down T cells before they can attack diseased cells.

"This is the first study to show that TRAILshort doesn't just block cell death — it also acts as a signaling molecule that directly suppresses T-cell activity," says Shahrzad Jalali, Ph.D., a research scientist at Mayo Clinic and lead author of the study. "That reveals an entirely new role for the protein in regulating the immune response."

Why TRAILshort is a potential target for new therapies

The findings suggest several potential therapeutic applications.

Researchers found that TRAILshort significantly reduced CAR-T therapy's ability to control tumors in preclinical models. Blocking the protein restored immune activity, suggesting that targeting it could be a new strategy to improve CAR-T therapy and other immunotherapies. The researchers also believe that TRAILshort could serve as a biomarker to help identify tumors more likely to respond to targeted therapies.

"Discovering the role of TRAILshort and how it inhibits CAR-T cells opens the door for a new therapeutic strategy to improve their activity," says Saad Kenderian, M.B. Ch.B., an oncologist at Mayo Clinic Comprehensive Cancer Center and study co-author. "This is an important step as we work to make CAR-T therapy more effective for patients with cancer."

Beyond cancer, researchers say TRAILshort  may eventually provide a way to selectively reduce harmful immune activity in autoimmune diseases or transplantation without broadly suppressing the immune system.

"In cancer, there's too much TRAILshort, so our goal is to get rid of it with antibodies that remove it. In autoimmune disease, there's not enough TRAILshort, so our goal is to deliver more," Dr. Badley says.

Additional studies are needed to determine whether these approaches are safe and effective in patients.

"What excites us most is that this discovery gives us a new, actionable way to regulate the immune system," Dr. Badley says. "By targeting TRAILshort, we may be able to strengthen immune responses against cancer and chronic infections or, in other diseases, reduce harmful immune activity."

This research is part of a broader effort at Mayo Clinic known as the Precure Research initiative. It focuses on developing tools to help clinicians detect and address disease-related changes earlier, before symptoms appear or conditions become harder to treat. This discovery identifies the molecular mechanism behind T-cell failure across cancer and chronic infection, giving researchers a defined target and a road map for therapeutic development.

For a complete list of authors, disclosures and funding, review the study.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

About Mayo Clinic Comprehensive Cancer Center
Designated as a comprehensive cancer center by the National Cancer Institute, Mayo Clinic Comprehensive Cancer Center is defining the cancer center of the future, focused on delivering the world's most exceptional patient-centered cancer care for everyone. At Mayo Clinic Comprehensive Cancer Center, a culture of innovation and collaboration is driving research breakthroughs in cancer detection, prevention and treatment to change lives.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post Researchers discover immune ‘off switch’ used by cancer cells  appeared first on Mayo Clinic News Network.

PHOENIX — An international phase 3 study performed at all three Mayo Clinic destination medical centers found that a new immunotherapy helped many patients with an aggressive form of bladder cancer keep their bladder instead of having it surgically removed. The treatment also kept many patients cancer-free for more than two years and caused mostly mild side effects. The findings were published in The Lancet Oncology.

Patients in the study had high-risk bladder cancer that had returned despite standard treatment with bacillus Calmette-Guérin (BCG). For these patients, surgery to remove the bladder is typically the recommended next step. The new immunotherapy treatment, called cretostimogene grenadenorepvec, produced a complete response, with no detectable signs of cancer in 75% of patients, with many of those responses lasting beyond two years.

"Until now, patients whose cancer returned after BCG therapy have had few effective options besides bladder removal," says Mark Tyson II, M.D., lead author of the study and a urologist at Mayo Clinic in Arizona. "This study shows we may be able to offer many of those patients another option without compromising cancer control."

Among patients whose cancer completely disappeared after treatment, about 60% remained cancer-free two years later. In one patient, the cancer has not returned for more than four years after completing treatment. Most treatment-related side effects were mild, temporary bladder symptoms, and researchers reported no severe treatment-related side effects.

"For patients, this isn't just about treating cancer — it's about preserving quality of life," says Dr. Tyson. "Avoiding bladder removal can have a profound impact on daily living. Seeing patients remain cancer-free for years while keeping their bladder is exactly the outcome we've been hoping to achieve."

The study included 115 patients treated at 41 medical centers across North America, Asia and Australia. Two years after starting treatment, an estimated 81% of patients had not needed surgery to remove their bladder. The researchers concluded that cretostimogene grenadenorepvec could become an important bladder-sparing treatment option for patients whose high-risk bladder cancer has returned after standard BCG therapy. They also noted that the treatment has not been directly compared with other bladder-sparing therapies in clinical trials.

The study was funded by CG Oncology. For a complete list of authors, disclosures and funding, review the study. The therapy remains investigational.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post Experimental immunotherapy may help patients with high-risk bladder cancer avoid bladder removal surgery appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A major national cooperative group clinical trial led by Mayo Clinic researchers found that continuing maintenance therapy with lenalidomide beyond two years after initial treatment for standard-risk multiple myeloma did not improve overall survival compared with stopping treatment after two years. The findings, published in The New England Journal of Medicine, may help physicians and patients make more informed decisions about the duration of maintenance therapy.

"Longer treatment is often assumed to be better, but that's not always the case," says Shaji Kumar, M.D., a Mayo Clinic hematologist, the study's primary investigator. "As therapies become more effective, it's increasingly important to determine not only which treatments work, but also how long patients need them." The researchers say the findings may reduce treatment burden and lower the costs associated with years of ongoing therapy for many patients.

"Knowing that maintenance therapy can safely end after a defined period may help reduce the demands of long-term treatment for patients," says S. Vincent Rajkumar, M.D., a hematologist at Mayo Clinic and chair of the ECOG-ACRIN Cancer Research Group’s Myeloma Committee which spearheaded the trial. "These findings support informed, shared decision-making between physicians and patients."

New treatments for multiple myeloma over the past two decades have improved survival, and some patients now experience long-term disease control. The study applies specifically to patients with standard-risk multiple myeloma who did not receive an upfront stem cell transplant. Additional studies are underway to determine the optimal duration of maintenance therapy for patients with high-risk disease and to explore whether treatment duration can be tailored using measurable residual disease testing.

"This study reminds us that clinical trials shouldn't only focus on adding new therapies," Dr. Kumar says. "They should also help us understand when treatment can safely stop."

The trial was designed and conducted by the ECOG-ACRIN Cancer Research Group with support from the U.S. National Institutes of Health’s National Cancer Institute, through its National Clinical Trials Network. Amgen provided additional support.  

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic-led study finds no improvement in overall survival from longer multiple myeloma maintenance therapy appeared first on Mayo Clinic News Network.

Mayo Clinic researchers are uncovering the earliest shifts in disease biology — long before symptoms appear — revealing how disease takes root and opening new possibilities to change its course. 

By the time a disease is diagnosed, it may have been developing silently for years. Along the way, the body leaves clues: proteins shift, metabolism changes, immune responses evolve, and environmental exposures leave measurable traces. Until recently, many of these early signals were impossible to detect.

Mayo Clinic researchers are now charting that hidden period between health and disease — a new frontier in medicine that could transform how conditions such as Alzheimer's disease, heart failure, pulmonary fibrosis, chronic liver disease and chronic kidney disease are identified and intercepted before symptoms emerge.

The new Mayo Clinic initiative, called Precure Research, brings together biospecimens, advanced biological data, environmental health research, longitudinal clinical data, wearable technologies and artificial intelligence (AI) to better understand how disease begins, predict risk earlier and create new opportunities for prevention.  

"Precure Research marks the beginning of the next era of scientific discovery and its translation into patient care."

Dr. Konstantinos Lazaridis

A glimpse of what's possible 

The initiative is already generating discoveries. Mayo Clinic scientists have identified inherited risks for cancer and cardiovascular disease in nearly 2,000 people — many of whom had no previous indication they were at risk. Other studies have shown that certain precancerous changes can be detected years before cancer develops. AI can help clinicians identify signs of pancreatic cancer years before diagnosis, while subtle biological changes linked to Alzheimer's disease begin decades before memory loss. Mayo Clinic researchers are using AI, genetics and wearable technologies to reveal inherited heart disease before heart failure.

"Precure Research marks the beginning of the next era of scientific discovery and its translation into patient care," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director of Mayo Clinic's Center for Individualized Medicine and director of Precure Research. "We are building the analytical and clinical tools needed to investigate questions that medicine has long recognized but has not been able to fully answer in ways that directly benefit patients."

The invisible years before diagnosis 

The initiative combines data from genes, proteins, metabolites, clinical records, wearable devices and environmental exposures to create a comprehensive view of how health changes and disease develops over time.

Underlying Precure Research is a new Mayo Clinic research ecosystem designed to study health and disease at an unprecedented scale. The initiative aims to build Mayo Clinic's largest integrated collection of biospecimens and scientific and health data to accelerate disease prediction and prevention.

Biological samples become data, and data becomes insight into the mechanisms of disease. Those insights drive the discovery of new biomarkers and therapies while informing smarter clinical trials.

AI helps researchers power that transformation, analyzing billions of data points simultaneously to reveal patterns that would otherwise remain invisible.

"Genomics showed us the blueprint, the underlying architecture of human biology," Dr. Lazaridis says. "Now we're watching that structure in motion — shifting, adapting, unfolding over time, shaped by the world around us and inside us, ultimately influencing the unique lives we each live." 

A lifetime of exposures

Disease is shaped by more than genetics alone. Across a lifetime, environmental and lifestyle exposures leave biological changes that accumulate over time. Scientists call this the exposome: the sum of those exposures and their effects on human biology.

These influences range from air, water and diet to pollutants, heavy metals, pesticides, physical activity, sleep, stress, noise and light.

"The air we breathe, the food we eat and the places we live leave a biological imprint," Dr. Lazaridis says. "Understanding those accumulated influences is essential to understanding why disease develops in one person and not another."

Researchers can now measure many of these exposures directly in blood and other biospecimens. Early efforts focus on heavy metals, pesticides and microplastics, linking those findings with geographic data to better understand how the places people live may influence their long-term health.

The exposome also captures protective influences, including nutrients and bioactive compounds that may support resilience and regulate inflammation, aging and metabolism.

A new vision for medicine 

The initial focus of Precure Research includes diseases of the brain, heart, kidneys, liver, and lungs, and their intersection with biological pathways such as inflammation, oxidative stress, aging and metabolic dysfunction.

Its long-term aim is to extend healthspan — the number of years people live in good health, free from chronic disease and disability — by addressing the drivers of chronic disease.

Precure Research is part of Mayo Clinic's Bold. Forward. strategy to Cure, Connect and Transform healthcare — helping define a future where disease is identified earlier, understood more completely and intercepted before it takes hold.

The post Mayo Clinic leaps into medicine’s next era with Precure Research  appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Researchers at Mayo Clinic have uncovered a previously hidden step in how the immune system prepares to fight cancer, a discovery that could help scientists develop more effective and longer-lasting cancer immunotherapies.

Published in Nature Communications, the study found that some cancer-fighting immune cells begin preparing for their role much earlier than previously believed — while they are still maturing in the thymus, an organ behind the breastbone that plays a central role in training T cells, particularly early in life.

The findings challenge the long-standing view that CD8-positive T cells — a type of immune cells that finds and destroys cancer cells — can leave the thymus in an inactive state and acquire their cancer-fighting abilities only after encountering threats elsewhere in the body. Instead, the research suggests that the thymus may help prepare these immune cells for rapid responses before they enter circulation.

CD8-positive T cells are among the immune system's primary cancer-fighting cells. The researchers found that PD-1 — a protein that is the target of several widely used cancer immunotherapy drugs — acts as a brake during their development, helping prevent these cells from becoming exhausted too quickly.

"Cancer immunotherapy has transformed treatment for many patients, but those responses don't always last," says Zhiming Mao, Ph.D., a recent graduate of Mayo Clinic Graduate School of Biomedical Sciences and first author on the paper. "We've discovered that the immune system may begin preparing for its fight against cancer much earlier than we realized. That insight could help us design therapies that are both more powerful and more durable."

PD-1 is already the target of several immune checkpoint inhibitor therapies used to treat a wide range of cancers, making the discovery particularly relevant to ongoing efforts to improve those treatments.

The findings may provide insight into why some immune responses against cancer are powerful but short-lived. Researchers say future therapies may need to strike a balance between boosting the immune system's attack on tumors and preserving the long-term function of cancer-fighting cells.

In preclinical models, removing PD-1 helped these immune cells control certain tumors more effectively. But the stronger response came at a cost: the cells became exhausted sooner, limiting their long-term cancer-fighting ability.

"Understanding how these immune cells are programmed at the earliest stages of development gives us a new way to think about improving cancer treatment," says Haidong Dong, M.D., Ph.D., an Iris and Winston Clement Professor of Research at Mayo Clinic and senior author of the study.

The findings come as researchers seek ways to make cancer immunotherapies more effective and longer lasting. While these treatments have transformed care for many patients, they do not work for everyone and can lose effectiveness over time.

The findings were based primarily on laboratory and preclinical model studies, and additional research will be needed to determine how they apply to patients.

For a complete list of authors, disclosures and funding, review the publication.

###

About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic researchers uncover critical link in the immune response to cancer appeared first on Mayo Clinic News Network.