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.  

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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

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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.

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ROCHESTER, Minn. — A Mayo Clinic-developed artificial intelligence (AI) model can help specialists detect pancreatic cancer on routine abdominal CT scans up to three years before clinical diagnosis. It identifies subtle signs of disease before tumors are visible, when curative treatment may still be possible. The findings, published in Gut, mark a milestone in Mayo Clinic's multiyear research effort to enable earlier detection of one of the deadliest cancers.

The study validates this next-generation AI model using data and workflows that mirror clinical practice, including CT scans from multiple institutions, imaging systems and protocols.

Researchers used the AI model to analyze nearly 2,000 CT scans, including scans from patients later diagnosed with pancreatic cancer — all originally interpreted as normal. The system, called the Radiomics-based Early Detection Model (REDMOD), identified 73% of those prediagnostic cancers at a median of about 16 months before diagnosis — nearly double the detection rate of specialists reviewing the same scans without AI assistance.

The advantage was even greater at earlier time points. In scans obtained more than two years before diagnosis, the AI identified nearly three times as many early cancers that would otherwise go undetected.

Pancreatic cancer remains one of the deadliest cancers because it rarely causes detectable signs in its earliest stages. More than 85% of patients receive a diagnosis after the disease has already spread, and five-year survival rates remain below 15%, according to the National Cancer Institute. Projections show it will become the second-leading cause of cancer-related death in the U.S. by 2030.

"The greatest barrier to saving lives from pancreatic cancer has been our inability to see the disease when it is still curable," says Ajit Goenka, M.D., the study's senior author, and a Mayo Clinic radiologist and nuclear medicine specialist. "This AI can now identify the signature of cancer from a normal-appearing pancreas, and it can do so reliably over time and across diverse clinical settings." 

REDMOD measures hundreds of quantitative imaging features that describe tissue texture and structure, capturing faint biological changes as cancer begins to develop. The model is designed to analyze CT scans already obtained for other reasons — particularly in high-risk patients, such as those with new-onset diabetes — and flag elevated risk before any visible mass appears. 

The model runs automatically without time-intensive manual preparation. The team validated the model across CT scans from multiple institutions, imaging systems and protocols, demonstrating consistent performance beyond a single dataset.

The model's predictions also remained stable over time. In patients with multiple scans, the AI produced consistent results months apart, supporting its use for longitudinal monitoring and early detection. 

"This AI can now identify the signature of cancer from a normal-appearing pancreas, and it can do so reliably over time and across diverse clinical settings."  - Dr. Ajit Goenka

Researchers are advancing this work into clinical testing through Artificial Intelligence for Pancreatic Cancer Early Detection, or AI-PACED. This prospective study evaluates how clinicians can integrate AI-guided detection into care for patients at elevated risk. The study combines AI analysis of routine imaging with longitudinal follow-up to assess performance, including early detection, false positives and clinical outcomes. 

This research is part of Mayo Clinic's Precure initiative, which aims to predict and prevent disease by identifying the earliest biological changes in the body before symptoms begin. It also reflects Mayo Clinic's Clinical Impact strategy, accelerating the translation of discovery into patient care. 

The study was supported by the National Institutes of Health, the Hoveida Family Foundation, the Mayo Clinic Comprehensive Cancer Center and the Champions for Hope Pancreas Cancer Research Program of the Funk-Zitiello Foundation. 

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

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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  

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These discoveries reflect progress across three major innovation efforts at Mayo Clinic. Mayo Clinic clinicians and scientists are working together to develop tools to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions through the Precure initiative. They are advancing new cures for end-organ failure beyond traditional transplantation as part of the Genesis initiative. They are also uniting clinical insight with cutting-edge engineering to deliver novel neurological diagnostics and therapies through the Bioelectronics Neuromodulation Innovation to Cure (BIONIC) initiative. 
 

1. 'Virtual clinical trials' may predict success of heart failure drugs 

Mayo Clinic researchers have created "virtual clinical trials" that advance the discovery of therapies while reducing time, cost and the risk of failed studies by combining advanced computer modeling with real-world patient data as part of the Precure and Genesis initiatives. Through one virtual clinical trial, they have developed a new way to predict whether existing drugs could be repurposed to treat heart failure, one of the world's most pressing health challenges. 

"Clinical trials will always remain essential," says Cui Tao, Ph.D., the Nancy Peretsman and Robert Scully Chair of Artificial Intelligence and Informatics and vice president of Mayo Clinic Platform Informatics. "But this innovation demonstrates how AI can make research more efficient, affordable and broadly accessible. Integrating trial emulation, simulation, synthetic trials and biomedical knowledge modeling opens the door to a new paradigm in translational science." 

2. New discovery may unlock regenerative therapies for lung disease

Mayo Clinic researchers have uncovered the molecular "switch" that directs a small but powerful set of cells that choose whether to repair tissue or fight infection, a discovery that could inform regenerative therapies for chronic lung diseases, which is part of Mayo Clinic's Genesis initiative.
 
"We were surprised to find that these specialized cells cannot do both jobs at once," says Douglas Brownfield, Ph.D., senior author of the study. "Some commit to rebuilding, while others focus on defense. That division of labor is essential — and by uncovering the switch that controls it, we can start thinking about how to restore balance when it breaks down in disease." 

3. Stem cells may offer new hope for end-stage kidney disease treatment

Mayo Clinic researchers found that injecting patients' own stem cells from fat cells into the vein before hemodialysis, a treatment for end-stage kidney disease, often helped prevent inflammation and vein narrowing. This could help millions of people tolerate dialysis longer, extending the time before they require a kidney transplant as part of the Mayo Clinic Genesis initiative. 

"This approach has the potential to improve outcomes for millions of patients with kidney failure, reduce healthcare costs and inform new clinical guidelines for dialysis access management if validated in larger clinical trials," says Sanjay Misra, M.D., a Mayo Clinic interventional radiologist. 

4. Mayo Clinic physicians map patients' brain waves to personalize epilepsy treatment

Using detailed maps of each patient's unique brain wave patterns, Mayo Clinic physicians can now pinpoint where stimulation is most effective, moving beyond the traditional one-size-fits-all approach to epilepsy treatment. This research is part of the BIONIC initiative.

"The long-term goal is to quiet the seizure network, so it is eventually forgotten. Reorganizing the neuronal network could move us beyond controlling seizures to actually curing epilepsy," says Nick Gregg, M.D., a Mayo Clinic neurologist. 

5. New genetic biomarker flags aggressive brain tumors

Mayo Clinic researchers found when meningiomas — the most common type of brain tumor — show activity in a gene called telomerase reverse transcriptase (TERT), it tends to recur more quickly, even if it looks low grade under the microscope. This is part of the Mayo Clinic Precure initiative. 

"High TERT expression is strongly linked to faster disease progression," says Gelareh Zadeh, M.D., Ph.D., a neurosurgeon at Mayo Clinic and senior author of the study. "This makes it a promising new biomarker for identifying patients who may be at greater risk of developing aggressive disease."

6. Mayo Clinic researchers discover the immune system's 'fountain of youth'

Mayo Clinic researchers have found that some older people maintain "immune youth" – a new term coined by Mayo researchers to explain a young immune system in someone over age 60.  
 
"We observed that these patients have very young immune systems despite being in their 60s and 70s. But the price they pay for that is autoimmunity," says Cornelia Weyand, M.D., Ph.D., a Mayo Clinic rheumatologist and clinician-scientist. This is part of the Mayo Clinic Precure initiative.

7. Mayo Clinic tools predict, identify and diagnose Alzheimer's, dementia quicker

Mayo Clinic researchers have developed new tools to estimate a person's risk of developing Alzheimer's disease years before symptoms appear as part of the Precure initiative and to help clinicians identify brain activity patterns linked to nine types of dementia, including Alzheimer's disease, using one scan. They also confirmed the accuracy of an FDA-approved blood test that can be used at outpatient memory clinics to diagnose the disease in patients with a range of cognitive impairment. 

"Every patient who walks into my clinic carries a unique story shaped by the brain's complexity," says David T. Jones, M.D., a Mayo Clinic neurologist. "That complexity drew me to neurology and continues to drive my commitment to clearer answers."

8. Mayo Clinic research improves dense breast cancer screening and early detection

Nearly half of all women in the U.S. have dense breast tissue, which can make detecting breast cancer difficult with a mammogram. Mayo Clinic researchers found that adding another test, called molecular breast imaging, or MBI, to a 3D mammogram, improved the ability to find cancer in dense tissue by more than double. 
 
"Our research focuses on detecting the most lethal cancers, which can include invasive tumors that grow quickly. If these are detected earlier, we likely can save more lives," says Carrie Hruska, Ph.D., a Mayo Clinic professor of medical physics and lead author of the study. 

9. Mayo Clinic researchers find 'sugar coating' cells can protect those typically destroyed in type 1 diabetes

After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, Mayo Clinic researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes. 

"A goal would be to provide transplantable cells without the need for immunosuppression," says Virginia Shapiro, Ph.D., a Mayo Clinic immunology researcher. "Though we're still in the early stages, this study may be one step toward improving care."

10. New study calculates autoimmune disease prevalence

Mayo Clinic researchers and collaborators have described — for the first time — the prevalence of autoimmune diseases in the U.S. Their research reports that about 15 million people are estimated to have one or more of 105 autoimmune diseases. The study also found that autoimmune diseases occur most often in women, and it identified the top autoimmune diseases by prevalence, sex and age. 
 
"Knowing the number of patients with an autoimmune disease in the U.S. is critical to assess whether these diseases are increasing or decreasing over time and with treatment," says DeLisa Fairweather, Ph.D., vice-chair of translational research for the Department of Cardiovascular Medicine at Mayo Clinic in Florida and corresponding author of the study.

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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 A Year of Discovery: 10 Mayo Clinic research breakthroughs moving medicine forward  appeared first on Mayo Clinic News Network.

JACKSONVILLE, Fla. — A major international study led by Mayo Clinic researchers and funded by the National Institutes of Health found that for people with severe carotid artery narrowing who haven't experienced recent stroke symptoms, a minimally invasive procedure called carotid artery stenting, combined with intensive medical therapy, significantly lowered stroke risk compared with medical therapy alone. Traditional surgery (carotid endarterectomy) did not show the same benefit. The research is published in The New England Journal of Medicine.

The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) is the largest study to date comparing current treatment approaches for this condition, caused by plaque buildup in the arteries supplying blood to the brain.

Carotid stenosis can lead to a stroke if plaque breaks off and blocks blood flow. Although surgery and stenting have long been used to open these arteries, newer medications and better risk factor control have raised questions about whether these procedures are still needed for people who don't have symptoms.

"Decades ago, surgery clearly helped prevent strokes in many patients," says Thomas Brott, M.D., a neurologist at Mayo Clinic in Florida and the study's senior author. "But medical therapy has improved so much that we needed to reexamine the balance between benefit and risk for people who have no symptoms."

The CREST-2 program consisted of two parallel, randomized clinical trials conducted at 155 medical centers in five countries, including Australia, Canada, Israel, Spain and the U.S. Each enrolled more than 1,200 adults with severe carotid artery narrowing of 70% or greater who had not had a stroke or transient ischemic attack (ministroke) in the past six months.

In one trial, participants received stenting plus intensive medical therapy or medical therapy alone. In the other, participants received endarterectomy plus medical therapy or medical therapy alone.

All participants received comprehensive medical care, including lifestyle coaching and medication as needed, to manage their blood pressure, low-density lipoprotein (LDL) cholesterol and diabetes, and to help them stop smoking.

Working with investigators from the University of Alabama at Birmingham, researchers analyzed the occurrence of stroke and death within 44 days of stenting or surgery. They also analyzed the occurrence of stroke over four years on the same side of the body as the narrowed artery.

The stenting trial found a significant reduction in stroke: over four years, 2.8% of patients treated with stenting and medical therapy had a stroke compared to 6% of those on medical therapy alone (roughly half the risk of stroke). However, in the endarterectomy trial, the difference in stroke rates (3.7% with surgery vs. 5.3% with medical therapy alone) was not statistically significant. Serious complications were uncommon with either procedure.  

The findings provide clearer guidance for physicians and patients considering a preventive procedure. Dr. Brott emphasizes personalized decision-making.

"For some patients — particularly those with more advanced narrowing or plaque that appears unstable or more likely to cause a blockage — stenting may offer added protection, while for others, medical therapy alone may be enough," he says.

Close follow-up and coordinated care helped all participants achieve and maintain significant improvements in their blood pressure and cholesterol levels.

Researchers will continue to track participants for long-term results. They are also studying whether imaging tools can help identify which patients benefit most from each treatment.

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

Related: Mayo Clinic Neurologists Lead International Study to Test Best Approach to Stroke Prevention

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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 Landmark Mayo Clinic study finds stenting reduces stroke risk in people with carotid artery narrowing appeared first on Mayo Clinic News Network.

While doctors are often focused on monitoring the health and vital signs of others, a new study had some tuning in to their own health and vital statistics as well. The results suggest that doing so may offer doctors real benefits to their own well-being, in a scalable way. 

Physicians who wore a smartwatch and had access to their personal health data — including information on their heart rate, sleep, breathing patterns and physical activity — reported greater resilience and 54% saw a reduction in the overall odds of burnout compared to those who did not receive a study smartwatch, according to new research published in JAMA Network Open. Mayo Clinic investigators conducted the study in collaboration with the University of Colorado School of Medicine.

"Advancing care starts with caring for those who deliver it. We're shaping a future where the well-being of our workforce is integral to the care we deliver."   - Colin West, M.D., Ph.D., Medical Director of Employee Well-Being at Mayo Clinic

Physician well-being is essential not only to personal health, but also to the quality of care patients receive. It's tied to job performance, patient safety, access to care and workforce sustainability.  

That’s why Mayo Clinic and others are prioritizing strategies to strengthen and sustain the well-being of healthcare professionals. 

How the smartwatch trial was designed and conducted 

The 12-month trial was conducted at Mayo Clinic and the University of Colorado School of Medicine. It included 184 physicians across specialties such as primary care, surgery, neurology and oncology. Researchers randomly assigned about half of the participants to wear a smartwatch for the full 12 months, while they gave the other half the watch during the study’s second half.

All participants received brief newsletters with general tips on smartwatch use and reminders to sync their devices. These resources aimed to support awareness of the tools and encourage engagement with personal health data.

Physicians in both study groups wore the device more than 70% of the time during the trial. Participants also completed validated well-being surveys at the beginning and end of the study. 

Participants could view their health data through a mobile app but were not prompted to take specific actions in response to it. Researchers say even this passive approach may help support well-being.  

Designing smarter tools for a healthy workforce

The study was co-designed and led by Arjun Athreya, Ph.D., an electrical and computer engineer in Mayo Clinic's Department of Molecular Pharmacology and Experimental Therapeutics; Colin West, M.D., Ph.D., medical director of Employee Well-Being at Mayo Clinic; and study Principal Investigator Liselotte Dyrbye, M.D., M.H.P.E., senior associate dean for faculty and chief well-being officer at the University of Colorado School of Medicine.  

"We're entering an era where wearable technology, when paired with thoughtful design and artificial intelligence methods that use the data, could help personalize well-being strategies in clinical settings," Dr. Athreya says. "This study shows we can support healthcare professionals with passive monitoring digital technologies with innovative engagement strategies to provide potentially helpful data without adding burden to their day."  

The researchers say this approach can offer timely support as part of a broader physician well-being strategy. 

"While this is an individually focused intervention, it offers an evidence-based way to support physicians in the short term, complementing longer-term efforts aimed at addressing systemic contributors to physician stress," says Dr. Dyrbye. 

Caring for caregivers: A vision for the future

Next steps for the researchers include evaluating long-term outcomes of the smartwatch project. They also plan to explore whether this approach can support other healthcare professionals.

"Advancing care starts with caring for those who deliver it," says Dr. West. "We’re shaping a future where the well-being of our workforce is integral to the care we deliver."   

The Physicians Foundation, Mayo Clinic's Center for Individualized Medicine, and the University of Colorado School of Medicine partly funded the study. Review the study for a complete list of authors, disclosures and funding details. 

The post Mayo Clinic smartwatch study reveals new path to boosting physician well-being appeared first on Mayo Clinic News Network.

Researchers are leading the nation in using powerful and precise radioactive drugs to treat people with complex cancers.  

ROCHESTER, Minn. — Mayo Clinic has treated the first person in the U.S. using a novel radioactive medicine for advanced breast cancer as part of an international multisite clinical trial.

The medicine used in this clinical trial contains actinium-225, a highly potent alpha-emitting radiopharmaceutical therapy that was first developed for a subtype of gastroenteropancreatic neuroendocrine tumors, which are rare and can form in the pancreas and the gastrointestinal tract. The alpha-emitting radiopharmaceutical therapy is intended to work by passing through the blood to stick to cancer cells, delivering powerful and precise radiation without harming healthy cells.

The Mayo Clinic researchers are the first to apply this therapy in America to a patient with metastatic breast cancer. The phase 1b/2 open-label trial is being conducted at all three academic Mayo Clinic sites in Rochester, Minnesota; Phoenix; Jacksonville, Florida; and approximately 20 other sites across the U.S. The first person treated was at Mayo Clinic in Florida.

The principal investigator at Mayo Clinic is Geoffrey Johnson, M.D., Ph.D., a professor of radiology and a leader in radiopharmaceutical therapies. He says these are innovative cancer treatments that use radioactive medicines designed to target and kill cancer cells with high precision.

Mayo Clinic has nearly 20 active radiopharmaceutical therapy clinical trials, with 10 more preparing to launch, targeting many different types of cancer. Mayo Clinic in Rochester treats more patients with modern radiopharmaceutical therapies, such as lutetium dotatate for neuroendocrine cancers and lutetium PSMA for prostate cancers, than any other center in the world.

Lutetium dotatate and lutetium PSMA are beta-emitting radiopharmaceuticals. They use beta particles, which are tiny subatomic particles, to radiate at a low level. In contrast, alpha-emitting radiopharmaceuticals use alpha particles that are 8,000 times more massive than beta particles, and travel only three cell diameters after they are emitted from the therapy.

"This means alpha emitters can deliver a much more powerful impact over a shorter distance. If you consider killing a cancer cell is like knocking down a brick wall, then the difference is like throwing a 10-pound dumbbell (beta) at the wall versus a fully loaded Mack truck (alpha)," says Dr. Johnson. "The alpha emitter's potential lies in its power and in its ability to precisely kill even a single cancer cell without injuring surrounding healthy tissue, making it a next-generation therapy."

In preclinical studies, data indicates actinium-225 DOTATATE that targets the somatostatin receptor subtype 2expression demonstrated feasibility and potential efficacy for treatment of ER+ metastatic breast cancer in the laboratory. The drug was developed by RayzeBio Inc., a Bristol Myers Squibb Company, the sponsor of the active phase 1b/2 clinical trial.

Study Title: Phase 1b/2 Open-label Trial of 225Ac-DOTATATE (RYZ101) in Subjects with Estrogen Receptor-positive (ER+), Human Epidermal Growth Factor Receptor 2 (HER2)-negative, Locally Advanced and Unresectable or Metastatic Breast Cancer Expressing Somatostatin Receptors (SSTRs) and Progressed After Antibody-drug Conjugates And/or Chemotherapy (TRACY-1)

• Descriptor: Phase 1b/2 open-label trial of 225Ac-DOTATATE (RYZ101) alone and with pembrolizumab in subjects with ER+, HER2-negative unresectable or metastatic breast cancer expressing SSTRs.
• Sponsor: RayzeBio Inc.
• Link: https://clinicaltrials.gov/study/NCT06590857

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

Media contact:

• Brittany Cordeiro, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic treats first person in the US with a novel radiopharmaceutical therapy for breast cancer appeared first on Mayo Clinic News Network.

For nearly three decades, Mayo Clinic researcher Christopher Evans, Ph.D., has pushed to expand gene therapy beyond its original scope of fixing rare, single-gene defects. That has meant systematically advancing the field through laboratory experiments, pre-clinical studies and clinical trials.

Several gene therapies have already received approval from the U.S. Food and Drug Administration (FDA), and experts predict that 40 to 60 more could be approved over the next decade for a range of conditions. Dr. Evans hopes a gene therapy for osteoarthritis — a form of arthritis affecting more than 32.5 million U.S. adults — will be one of them.

Recently, Dr. Evans and a team of 18 researchers and clinicians reported the results of a first-in-human, phase 1 clinical trial of a novel gene therapy for osteoarthritis. The findings, published in Science Translational Advances, demonstrated that the therapy is safe, achieved sustained expression of a therapeutic gene inside the joint and offered early evidence of clinical benefit.

"This could revolutionize the treatment of osteoarthritis," says Dr. Evans, who directs the Musculoskeletal Gene Therapy Research lab at Mayo Clinic.

In osteoarthritis, the cartilage that cushions the ends of bones — and sometimes the underlying bone itself — degenerates over time. It is a leading cause of disability, and notoriously difficult to treat. "Any medications you inject into the affected joint will seep right back out in a few hours," says Dr. Evans. "As far as I know, gene therapy is the only reasonable way to overcome this pharmacologic barrier, and it's a huge barrier." By genetically modifying cells in the joint to produce their own pharmacy of anti-inflammatory molecules, Evans aims to engineer knees that are more resistant to arthritis.

The Evans laboratory found that a molecule called interleukin-1 (IL-1) plays an important role in fueling inflammation, pain and cartilage loss in osteoarthritis. As luck would have it, the molecule had a natural inhibitor, aptly named the IL-1 receptor antagonist (IL-1Ra), that could form the basis of the first gene therapy for the disease. In 2000, Dr. Evans and his team packaged the IL-1Ra gene into a harmless virus called AAV, which they tested in cells and then pre-clinical models. The results were encouraging.

In pre-clinical testing, his collaborators at the University of Florida demonstrated that the gene therapy successfully infiltrated the cells that make up the synovial lining of the joint as well as the neighboring cartilage. The therapy protected the cartilage from breakdown. In 2015, the team got investigational new drug approval to start human testing. But regulatory hurdles and manufacturing challenges kept them from injecting their first patient for another four years. Mayo Clinic has since established a new process for accelerating clinical trial activation that could help researchers launch studies more quickly.

In the recent study, Dr. Evans and his team gave the experimental gene therapy to nine patients with osteoarthritis, delivering it directly into the knee joint. They found that the levels of the anti-inflammatory IL-1Ra increased and remained elevated in the joint for at least a year. Participants also reported reduced pain and improved joint function, with no serious safety issues. Dr. Evans says the findings suggest the treatment is safe and may offer long-lasting relief from osteoarthritis symptoms. "This study provides a highly promising, novel way to attack the disease," he says.

Dr. Evans has co-founded an arthritis gene therapy company called Genascence to drive the project forward. The company just completed a larger phase Ib study and is in discussions with the FDA about launching a pivotal phase IIb/III clinical trial to evaluate the therapy's effectiveness, the next step before FDA approval for the therapy.

Review the study for a complete list of authors, disclosures and funding. 

Additional resources:

• Pushing the limits of gene therapy for osteoarthritis

The post Progress in gene therapy offers hope for long-term knee pain relief appeared first on Mayo Clinic News Network.

September marks the start of soybean harvest in Mankato, Minnesota, a busy time of year when farmers can't afford to be away from their fields for long. So, when Craig Smith, 66, began experiencing a burning sensation while urinating, he went to his family physician right away.

He was prescribed antibiotics, but his symptoms worsened. When Smith began to pass blood, his wife insisted that they drive straight to Mayo Clinic in Rochester — about an hour and a half away. There, Mayo Clinic physicians diagnosed him with metastatic urothelial cancer, or bladder cancer, which had spread to his spine.

Smith recalls receiving a phone call late that night from his Mayo Clinic doctor, who asked him if he wanted to just maintain his health for a few years or cure his cancer.

"I said, 'I'd like you to cure it,'" says Smith.

Seeking a bladder cancer cure

Smith's father had been a farmer, which was his dream too. But his father suggested he gain additional skills to supplement his farming income. Following his father's advice and encouragement from his high school welding teacher, Smith pursued his teaching certificate in welding. What he initially thought would be five or six years of teaching turned into a 45-year career developing welding programs at several local schools while also raising cattle and growing soybeans and corn on his 2,000-acre farm. Through his welding programs, he has trained several welders now employed by local manufacturing companies.

After his diagnosis in 2023, Smith took a hiatus from teaching and farming to focus on his cancer treatments at Mayo Clinic Health System in Mankato, which included chemotherapy, radiation and immunotherapy.

Metastatic urothelial cancer that has spread beyond the bladder usually is considered incurable and inoperable. However, Smith responded well to chemotherapy and radiation to his spine, which made his oncologist, Jacob Orme, M.D., Ph.D., and urologist, Paras Shah, M.D., consider Smith for a new, surgical approach to treatment.

Smith proceeded with the proposed surgery and had his bladder, prostate and 36 lymph nodes removed.

"In Mr. Smith's bladder, we found viable cancer cells that would have led to a relapse. Now, however, he is nearly two years from diagnosis and remains disease-free," says Dr. Shah.

Smith's positive response to treatment and surgery has spurred a clinical trial testing this aggressive approach in other bladder cancer patients. Currently, 17 participants are enrolled, and the results so far have been promising.

Advances in cancer treatment, such as immunotherapy that harnesses the body's immune system to fight cancer and the identification of biomarkers in the blood or urine that show how well a patient is responding to treatment, are helping the physicians select who will benefit most from surgery.

"The impetus for this study is to attack the cancer from multiple approaches, including treatments that cover head-to-toe and treatments that are directed right at the source tumor," says Stephen A. Boorjian, M.D., who is the David and Anne Luther Chair of Urology at Mayo Clinic and a lead proponent of the study.

"We want to remove the root of the cancer after we've burned off the leaves," adds Dr. Orme.

A team of researchers, physicians and clinical trials staff expedited the clinical trial through an accelerated pathway called a Rapid Activation Trial. It's part of a larger effort at Mayo Clinic to launch new clinical trials swiftly and effectively.

"Shortening activation timelines allows us to make a difference to more patients and their families," says Michelle Monosmith, Mayo Clinic Office of Clinical Trials operations administrator.

The study is supported by a generous donation by Ronald J. and Carol T. Beerman to Mayo Clinic and has been prioritized by Dr. Boorjian and Chair of Oncology Elisabeth Heath, M.D., to achieve more cures for men and women with bladder cancer.

"Our only goal is to help our patients live better and longer," says Dr. Orme.

That's what Smith plans to do as he continues to farm, teach and spend time with his family.

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For Stewart, the desire to become a scientist began at home. From a young age, she was aware of her father's diagnosis with cancer and the struggles he faced as his body became resistant to some treatments. Four years ago, when she became a predoctoral student at Mayo Clinic Graduate School of Biomedical Sciences, she chose a research project addressing blood cancers like his.

Working under the mentorship of Mayo Clinic hematologist oncologist Saad Kenderian, M.B., Ch.B., she has studied specially engineered immune cells, called chimeric antigen receptor-T cells or CAR-T cells, that are used to treat blood cancers like leukemia. She identified a signaling protein that, when neutralized, boosts the function of CAR-T cells by keeping them from reaching a state of "exhaustion." She and Dr. Kenderian's team published their findings in Nature Communications.

Stewart was delighted to learn that the journey of the new concept didn't stop there. "The approach she explored is novel, and her findings show there's a solid rationale to see whether it may help patients," says Dr. Kenderian.

'An incredible learning curve'

As the opportunity to advance the idea has emerged, Stewart has begun to learn about developing a clinical trial. "It's been an incredible learning curve," she says of taking a discovery beyond the lab space.

Close collaboration between researchers and clinicians at Mayo is what makes the steps of translation — from discovery to the clinic — happen efficiently, says Dr. Kenderian. Students like Stewart have opportunities to learn about the steps that shape clinical trials to bring new treatments to patients.

She and Dr. Kenderian met with a panel of Mayo physicians to get feedback about the design of a phase 1 clinical trial, which tests the safety of a new approach in a small cohort of patients who are interested in participating. "It was a great opportunity for me to hear how things are translated into the clinic, what questions and concerns clinicians may have, and how feasible our approach may be," she says.

"CAR-T cell therapy can be remarkable for some patients who have no other options, and the hope is to develop a more durable, lasting approach. This part of the research is still in early stages, but it's a very exciting project, and I feel lucky to be a part of it."

'Beyond what seemed possible'

Many Ph.D. students at Mayo Clinic are preparing for future careers in academia and industry. Another way they can learn about research that involves human participants is through an internship at Mayo Clinic's Office of Clinical Trials. Working with Mayo's clinical trials coordinators, students have followed a clinical trial underway and learned about designing a study that provides meaningful data and protects the rights, safety and welfare of patients who volunteer to participate.

But for some students, like Olivia Sirpilla, who is graduating in May from Mayo Clinic Graduate School of Biomedical Sciences, a long series of successful experiments in Dr. Kenderian's lab has opened the door to the next stages. Sirpilla's Ph.D. research looked at developing specially engineered stem cells from fat tissue as a treatment to calm the inflammation that occurs in immune diseases.

The team's results, published in Nature Biomedical Engineering, have set the stage for two potential clinical trials. One may be applicable to graft-versus-host-disease, an immune system complication that can occur after a stem cell transplant. The findings also may be applicable to the treatment of inflammatory bowel disease, particularly for patients who no longer respond to medications.

To design these clinical trials, Sirpilla and Dr. Kenderian are working with teams of Mayo clinicians who specialize in these disorders and their standard treatments. "I chose to come to Mayo Clinic for my Ph.D. to conduct lab research that would be highly translational," she says. "But to spend my thesis work developing a new cell therapy platform that is ready to be translated into a clinical trial is beyond what I thought possible in a Ph.D."

Research that reaches patients' daily lives  

Stephanie Zawada began her Ph.D. with an interest in computational approaches to research, but she has always strived to make advances that reach patients' daily lives.

Her thesis project aimed to help physicians assess people who have experienced a stroke and may be at risk for another.  She engaged two Ph.D. mentors who shared their expertise: Bart Demaerschalk, M.D.,  and  Bradley Erickson, M.D., Ph.D. Dr. Demaerschalk is a professor of neurology who treats patients with stroke at Mayo Clinic in Arizona and has a longstanding interest in digital health and using telemedicine to reach remote patients, and Dr. Erickson is a professor of radiology who leads artificial intelligence studies at his lab at Mayo Clinic in Minnesota.

Zawada "took a very innovative approach, exploring digital tools that may help a healthcare team continue to monitor and evaluate patients who have been discharged from the hospital but remain at risk for stroke recurrence," says Dr. Demaerschalk.

First, Zawada scoured available databases to identify attributes, including mood changes and sleep patterns, that can signal an oncoming stroke and can be captured by smartphone-based technology known as "wearables." Then she worked with her mentors and members of the Center for Digital Health to develop a pilot clinical trial with patients who volunteered to participate in a study from their homes.

Zawada designed a study that met the requirements of an institutional review board, or IRB, to address regulatory compliance. Aiming to get information from a "real-world" setting — where patients interact with app-based tools and the tools account for the range of daily activities — added logistical and mathematical complexity to the project. She worked with Dr. Demaerschalk and Mayo Clinic hospital-based stroke teams to recruit a cohort of 35 patients who gave consent to be part of the clinical trial.  

"Interacting with patients and hearing their concerns is the best way to advance useful technologies," Zawada says of designing the trial. "You want the clinical trial process to be as simple as possible for participants, and the only way to learn what tools and designs can make their lives better is to listen to them."

Her results showed that several behavioral and mood changes related to cerebrovascular disease can be captured with the use of wearable devices, even from patients going about their daily routines far from a hospital. The approach will need further investigation as a strategy to improve care and in the development of clinical trial measures, but the training to conduct a clinical trial is something that Zawada will take to the next stages of her career.

"Setting up a clinical trial is a complex process and really involves a team," says Zawada, who graduates in May and plans to continue researching wearables for patients who have other severe health conditions. "My thesis project was a multi-site collaborative effort — putting together the clinical questions, the new technology and the data analysis, the connection with patients — it's why I came to train at Mayo in the first place. As a student, I couldn't have done this project anywhere else."

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