Late-breaking abstract featured at ASCO 2025

ROCHESTER, Minn. — Colon cancer is the third most prevalent form of cancer in the U.S., and while screening has helped detect and prevent colon cancer from spreading, major advancements in treating colon cancer have lagged.

Now, new research led by Mayo Clinic Comprehensive Cancer Center found that adding immunotherapy to chemotherapy after surgery for patients with stage 3 (node-positive) colon cancer — and with a specific genetic makeup called deficient DNA mismatch repair (dMMR) — was associated with a 50% reduction in cancer recurrence and death compared to chemotherapy alone. Approximately 15% of people diagnosed with colon cancer exhibit dMMR and, to date, these tumors appear less sensitive to chemotherapy. The results of the multi-center study were presented during a plenary session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

"The findings from our study represent a major advance in the adjuvant treatment of dMMR stage 3 colon cancer and will now change the treatment for this type of cancer," says oncologist Frank Sinicrope, M.D., who led the study. "It's extremely rewarding to be able to offer our patients a new treatment regimen that can reduce the risk of recurrence and improve their chances of survival."

Until now, the standard treatment after surgery for any stage 3 colon cancer has been chemotherapy. However, the researchers note that approximately 30% of patients experience cancer recurrence despite this treatment. 

Watch: Dr. Frank Sinicrope discusses Mayo Clinic immunotherapy study

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The clinical trial enrolled 712 patients with dMMR stage 3 colon cancer that had been surgically removed and who had cancer cells in their lymph nodes. The immunotherapy given in this study was an immune checkpoint inhibitor, known as atezolizumab, which activates one's immune system to attack and kill cancer cells, which are responsible for cancer recurrence and spread. The patients — who lived in the U.S. and Germany — received chemotherapy for six months along with immunotherapy and then continued with immunotherapy alone for another six months.

Dr. Sinicrope and others previously studied patients with colon cancer whose cells are unable to repair errors during DNA replication that create a nucleotide mismatch, a condition called dMMR. They noted that these patients' tumors showed a striking increase in inflammatory cells within the tumor, including those that express the target of immune checkpoint inhibitors. This sparked the idea of using immune checkpoint inhibitors to make the immune cells more effective in attacking and killing the cancer cells.   

Based on the data from this study, Dr. Sinicrope recommends this combination of immunotherapy and chemotherapy treatment to be the new standard treatment for stage 3 deficient mismatch repair colon cancer. The research team plans to approach the National Comprehensive Cancer Network, a nonprofit organization consisting of 33 leading cancer centers, including Mayo Clinic, with this recommendation.  

The study included patients with Lynch syndrome, the most common form of hereditary colon cancer, as these patients can have tumors that show deficient mismatch repair (dMMR).

"We're changing the paradigm in colon cancer treatment. By using immunotherapy at earlier stages of disease, we are achieving meaningful benefits for our patients," says Dr. Sinicrope.

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

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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:

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

The post Immunotherapy boosts chemotherapy in combating stage 3 colon cancer appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic Comprehensive Cancer Center researchers will present their latest oncology findings at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, scheduled to be held May 30–June 3 at the McCormick Place Convention Center in Chicago. The event, recognized as one of the largest gatherings in the field of cancer research, will feature 59 Mayo Clinic-authored abstracts highlighting advancements in cancer care.

Among the standout presentations are practice-changing studies focused on chemotherapy approaches, artificial intelligence (AI) applications in oncology, cancer care at home and new therapies for breast cancer and melanoma — all focused on improving treatment options for patients with cancer.

Highlights include:

Plenary Session: Randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage 3 deficient DNA mismatch repair (dMMR) colon cancer (Alliance A021502; ATOMIC)
Presentation time: Sunday, June 1, 1:05 to 1:17 p.m. CDT
Session title: Special Sessions
Presenter: Frank Sinicrope, M.D., medical oncologist and gastroenterologist

Clinical Science Symposium: Perception and concerns of the hematology and oncology (HemOnc) workforce about artificial intelligence (AI) in clinical practice (CliPr) and medical education (MedED)
Presentation time: Saturday, May 31, 2:03 to 2:15 p.m. CDT
Session title: The Future Is Now: Innovations in Medical Education
Presenter: Guilherme Sacchi de Camargo Correia, M.D., oncology fellow (senior author is Rami Manochakian, M.D., thoracic medical oncologist)

Oral Abstract Session: Tissue-free circulating tumor DNA assay and patient outcome in a phase 3 trial of FOLFOX-based adjuvant chemotherapy (Alliance N0147)
Presentation time: Friday, May 30, 3:57 to 4:09 p.m. CDT
Session title: Gastrointestinal Cancer — Colorectal and Anal
Presenter: Frank Sinicrope, M.D., medical oncologist and gastroenterologist

Oral Abstract Session: [212Pb]VMT-α-NET therapy in somatostatin receptor 2 (SSTR2) expressing neuroendocrine tumors (NETs): Dose-limiting toxicity (DLT) observation participants after one-year follow-up and preliminary report for expansion participants.
Presentation time: Friday, May 30, 4:09 to 4:21 p.m. CDT
Session title: Developmental Therapeutics — Molecularly Targeted Agents and Tumor Biology
Presenter: Thorvardur Halfdanarson, M.D., medical oncologist       

Oral Abstract Session: NeoACTIVATE arm C: Phase II trial of neoadjuvant atezolizumab and tiragolumab for high-risk operable stage 3 melanoma
Presentation time: Tuesday, June 3, 2025, 10:45 a.m. to 10:57 a.m. CDT
Session title: Melanoma/Skin Cancers
Presenter: Tina Hieken, M.D., breast and melanoma surgical oncologist

Poster Session: Cancer Care Beyond Walls (CCBW): A randomized pragmatic trial of home-based versus in-clinic cancer therapy administration
Session time: Sunday, June 1, 9 a.m. to noon CDT
Session title: Care Delivery and Quality Care
Presenter: Roxana Dronca, M.D., medical oncologist and the site deputy director of Mayo Clinic Comprehensive Cancer Center in Florida

Poster Session: A pilot single-arm, pragmatic trial in progress of in-home versus in-clinic subcutaneous nivolumab administration through Cancer Care Beyond Walls (CCBW) program (connected access and remote expertise)
Session time: Sunday, June 1, 9 a.m. to noon CDT
Session Title: Care Delivery/Models of Care
Presenter: Dina Elantably, M.B., B.CH., oncology fellow (senior author is Roxana Dronca, M.D., medical oncologist and the site deputy director of Mayo Clinic Comprehensive Cancer Center in Florida)

Poster Session: Initial results of MC200710 investigating therapeutic vaccine (PDS0101) alone or with pembrolizumab prior to surgery or radiation therapy for locally advanced HPV associated oropharyngeal carcinoma, a phase 2 window of opportunity trial
Session time: Monday, June 2, 9 a.m. to noon CDT
Session title: Head and Neck Cancer
Presenter: David Routman, M.D., radiation oncologist

Poster Session: ALISertib in combination with endocrine therapy in patients with hormone receptor-positive (HR+), HER2-negative (HER2–) recurrent or metastatic breast cancer: The phase 2 ALISCA-Breast1 study
Session time: Monday, June 2, 9 a.m. to noon CDT
Session title: Breast Cancer — Metastatic
Presenter: Tufia Haddad, M.D., medical oncologist

Poster Session: Estrogen receptor expression in residual breast cancer following neoadjuvant chemotherapy
Session time: Monday, June 2, 9 a.m. to noon CDT
Session title: Breast Cancer — Local/Regional/Adjuvant
Presenter: Sarah Premji, M.D., oncology fellow (senior author is Matthew Goetz, M.D., breast medical oncologist, and the Erivan K. Haub Family Professor of Cancer Research Honoring Richard F. Emslander, M.D.)

For more information about 2025 ASCO visit: https://www.asco.org/annual-meeting.

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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 on-site at ASCO:

• Kelley Luckstein, Mayo Clinic Communications, 507-202-8655, luckstein.kelley@mayo.edu

The post Mayo Clinic experts present key cancer research findings at ASCO appeared first on Mayo Clinic News Network.

Many people have no symptoms, but in some cases, the infection can spread to the brain, bones, or spine and become life-threatening. Because symptoms often mimic the flu or pneumonia, valley fever is frequently misdiagnosed. Current tests can be slow and unclear, delaying the right treatment.

Dr. Thomas Grys, a Mayo Clinic researcher working in collaboration with Arizona State University, is developing next-generation tools to detect valley fever earlier and more accurately. The goal is to help patients get answers and early treatment.

Here's how Mayo Clinic is advancing the future of valley fever diagnoses.

Watch: Faster diagnosis for valley fever with new test in development

Journalists: Broadcast-quality video (1:55) is in the downloads at the end of this post. Please courtesy: "Mayo Clinic News Network." Read the script

From the vast deserts of the Southwest to the laboratory of Dr. Thomas Grys at Mayo Clinic in Arizona, microscopic fungal spores of valley fever are the focus of research.

"Spores are kind of like the seeds of the fungus. They are very durable. They can exist and persist in the environment. And they're tiny, so they float in the air and we can breathe them in," says Dr. Grys.

Each year, up to 3% of people in the Southwest are exposed to infection and develop antibodies, no matter how long they’ve lived there. Dr. Grys says valley fever infections are common, but the current diagnostics could be better.

"And one of the most frustrating things is, if someone has symptoms of a brain infection with valley fever, it's difficult to confirm whether they have that in their brain or not, and if they do, they're going to be on antifungal medications for the rest of their life. We cannot cure it from the brain," he says.

Rapid test

That's why this rapid antibody test being developed — similar in format to a COVID-19 test —  is so important.

"The test we're working on can detect antibodies in 10 minutes. We still have to wait for the body to respond to the fungus, but once it does, we can provide answers in 10 minutes," Dr. Grys says.

The shortened time to detect fungal antibodies means that answers could be back in time to inform patient care during their visit.

"Some patients come in four or five times until they figure out what's happening. Every single time going to the doctor, you have to find transportation, you might have to find childcare. It's a burden to have to go in," he says.

And for patients, Dr. Grys says the rapid antibody test could change the paradigm.

"The median time to diagnosis is 23 days. Half of the people take more than 23 days to find out they have valley fever. If we can get testing that's more rapid and get answers faster, people will be more prone to test because a decision can be made while the patient is there," he says.

Availability

The antibody test is licensed to a startup company, and the test is expected to be commercially available for laboratory use by the end of 2025.

Treatment

For advanced cases of valley fever, the Cocci Clinic at Mayo Clinic in Arizona offers a coordinated, multispecialty team — including infectious diseases specialists, pulmonologists, neurologists, dermatologists and cardiothoracic surgeons. 

The post (VIDEO) Faster diagnosis for valley fever: New test in development appeared first on Mayo Clinic News Network.

A recent Mayo Clinic study revealed how telehealth can be a powerful tool to enhance patient well-being when strategically applied in healthcare delivery.

The study showed that patients who received remote monitoring support after discharge did significantly better and needed less follow-up care compared to patients without remote monitoring. 

"This study explores the relationship between hospitals' implementation of telehealth services and the impact on patients' social needs," says Aaron Spaulding, Ph.D., a healthcare researcher at the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery and senior author of the study.  "The study aims to determine the effects on four key outcomes: better patient health, reduced hospital service use, lowered healthcare costs and enhanced community health."

The study also found that when patients used online therapy, they were much more likely to say their overall health in the community had improved compared to those who did not receive such services.

The study investigators say that the findings provide a closer look into telehealth's versatile ability to address social determinants of health and offer a path for future research into ways to enhance overall patient-centered care.

"There has been significant research identifying gaps in healthcare due to social determinants of health,"

says Dr. Spaulding. "The publication team has explored various avenues to understand the barriers to access and areas that inadvertently worsen outcomes related to social determinants."

Dr. Spaulding notes that telehealth, when combined with in-person visits, has the potential to help create a more integrated approach to healthcare delivery, but says that it should be treated as a complementary tool and that any approach needs to be personalized.

"Different patients require varying levels of care, and while our systems are improving, some patients may benefit from telehealth, while others may prefer in-person care," says Dr. Spaulding.  "Additionally, a combination of approaches might be beneficial for certain individuals."

Looking ahead, the researchers emphasize the need to continue focusing on strategically and thoughtfully deploying telehealth services in patient care.

"We must continue to assess the most effective ways to use telehealth to benefit patients," says Dr. Spaulding. "This evaluation should consider both hospital-specific outcomes, such as readmissions and emergency department visits, as well as patient experience and patient-reported outcomes."

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

About Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery

The Mayo Clinic, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, collaborates with clinical areas across Mayo to create and evaluate data-driven solutions to transform the health and healthcare experience for patients, staff and communities. It drives continuous improvement of Mayo Clinic as a learning health system, enabling safe, evidence-based, high-quality care.

The post Harnessing telehealth to enhance patient care appeared first on Mayo Clinic News Network.

Dr. Ethel Aguirre Flores broke her first bone before she learned to walk. Since then, she has endured more than 125 other fractures — femurs, arms, ribs and vertebrae. Her medical chart includes 41 surgeries and six metal rods that hold her limbs together. 

Her most recent fracture happened just months ago when she broke her toe while dancing. Not long before that, her femur snapped while she was simply walking. 

But through it all, her determination, perseverance and commitment to helping others have remained unbreakable. 

Watch: A Mayo Clinic resident's unbreakable journey

Journalists: Broadcast-quality video pkg (4:25) is in the downloads at the end of the post. Please courtesy: "Mayo Clinic News Network." Read the script. 

Born with osteogenesis imperfecta, a rare genetic disorder also known as brittle bone disease, Dr. Aguirre Flores is now completing her residency in medical genetics and genomics at Mayo Clinic.  

She came to Mayo specifically to study under one of the leading physician-scientists in the world focused on treating brittle bone disease at the molecular level. Dr. David Deyle, a clinical geneticist, has spent nearly 30 years studying the condition's genetic underpinnings and building the expertise needed to do what medicine has never done: develop a therapy that repairs it at its source. In addition to leading research, Dr. Deyle devotes most of his time to patient care, seeing nearly 30 patients with rare genetic disorders each week. 

"Our goal is to correct the underlying genetic defect of osteogenesis imperfecta," Dr. Deyle says. "That means going directly into the genome, because you can't transplant bone stem cells. You have to repair them at their source." 

Dr. Deyle is developing gene therapy to target the genetic mutation that disrupts collagen, the protein that gives bones their strength. The mutation produces a faulty form of collagen, which leaves bones weak and prone to fractures. 

Dr. Deyle's team is pursuing two primary approaches. One uses gene editing, such as CRISPR, a tool that precisely cuts and modifies DNA, to eliminate the faulty genetic instructions. The other uses a small molecule therapy to strengthen bone density without altering DNA. Both approaches are inching closer to clinical trials. 

"We can do this in the lab," Dr. Deyle says. "The challenge is delivery — getting the therapy directly into the bone." 

That same precision guides the team's work across a range of rare conditions. One project involves classical Ehlers-Danlos syndrome, a connective tissue disorder marked by fragile skin and poor wound healing. Dr. Deyle's team is using a combination of gene and cell therapies to give patients a second working copy of the gene they're missing. The modified cells are then reintroduced into the body to aid healing at the site of injury. 

Another effort targets neurofibromatosis, a disease that causes tumors to grow along nerves. Dr. Deyle's team was the first to use a viral vector to deliver a key therapeutic protein. The method, which relies on a modified virus to transport treatment directly into cells, could help advance gene therapies for other rare conditions. 

While the science is groundbreaking, the stories behind it are equally compelling. Some of the most determined minds behind this research in Dr. Deyle's lab know these conditions firsthand, including Dr. Aguirre Flores. She's the third person with brittle bone disease to train under his guidance. 

"People with this condition know what it means to face setbacks," Dr. Deyle says. "That gives them a focus you can't teach. You can see it in Dr. Aguirre Flores — she's a fighter, and she pours everything she has into this work because of what she's lived through." 

Dr. Aguirre Flores grew up in northern Mexico, the only daughter in a family of four children. Her parents encouraged her to chase every dream.  

"They would always let me know anything's possible," she says. "You can do anything you want." 

She swam competitively, earning medals despite broken ribs. She painted with casts on her legs.  

At age 8, she met a care team in Texas that changed her view of what care could be. That's when she knew she wanted to become a doctor. 

"They saw me as a child first, not just a diagnosis," Dr. Aguirre Flores says. "That changed everything."  

Now, she brings that same perspective to her own career.  

"I know what these children are going through. I want to help children with congenital disorders as a whole and help them live their childhood to the best," Dr. Aguirre Flores says. 

In June, she will graduate from Mayo Clinic's Medical Genetics and Genomics Residency and begin a new role as a pediatric geneticist in Texas. 

"I hope that my story brings hope and inspires others to not put limits on themselves," Dr. Aguirre Flores says. "And to always go after your dreams." 

The post (VIDEO) From 125 fractures to the front lines of discovery: A Mayo Clinic resident’s unbreakable journey  appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Millions of people are affected by chronic dry mouth, or xerostomia, an agonizing side effect of damaged salivary glands. While chemotherapy and radiation treatment for head and neck cancer are the most common causes of this, aging, certain medications and other factors, including diabetes, stroke, Alzheimer's disease and HIV/AIDS, can also cause chronic dry mouth. Currently, there is no cure for it.

Mayo Clinic researchers have established the world's first biobank of human salivary gland tissue-organoids that opens the door to research to find a cure.

"This unique biobank resource overcomes a major barrier we've faced in the field, namely: limited access to standardized salivary specimens suited for salivary gland regeneration research. This collection provides a foundation for regenerative therapy development, especially for radiation-induced chronic dry mouth," says Nagarajan Kannan, Ph.D., lead author of the study published in NPJ Regenerative Medicine. Dr. Kannan is also the director of the Mayo Clinic Stem Cell and Cancer Biology Laboratory.

Nearly 70% of patients with head and neck cancer who are undergoing radiation therapy experience permanent damage to their salivary glands. People with this condition experience diminished quality of life from a constant feeling like cotton is lining their mouths. Besides being uncomfortable, chronic dry mouth can lead to difficulties with chewing, tasting, speaking and swallowing. It also can cause tooth decay.

"Chronic dry mouth can extend long after radiation treatments are complete. It's among the top concerns I hear from patients with head and neck cancer. Unfortunately, there aren't many therapeutics available commercially for these patients," says co-author Jeffrey Janus, M.D., an ear, nose and throat specialist at Mayo Clinic in Florida.

One promising avenue of research is the cultivation of rare regenerative cells to greater numbers that can help people someday heal and grow new, healthy salivary gland cells. The biobank consists of specimens collected from 208 donors. From this repository, researchers have already found biomarkers for mature, saliva-producing cells, and with the help of a high-resolution protein map, they have identified the potential tissue origin of rare, self-renewing salivary cells.

The research team also developed a radiation injury model, which paired with the biobank, provides an integrated platform to discover new, personalized regenerative biotherapeutics.

This is a collaboration between Mayo Clinic Center for Regenerative Biotherapeutics, Department of Laboratory Medicine and Pathology and Department of Otolaryngology.

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

###

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:

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic researchers develop first salivary gland regenerative biobank to combat chronic dry mouth 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.

The post Farmer inspires new potential bladder cancer treatment appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A new discovery by Mayo Clinic researchers could mean more donor hearts are available for heart transplant, giving more people a second chance at life.

In findings published in Nature Cardiovascular Research, a team led by Mayo Clinic cardiac surgeon Paul Tang, M.D., Ph.D., identified a biological process that contributes to donor heart injury during cold storage. The researchers found that a drug already used to treat heart conditions can prevent this damage.

Heart transplantation is the most effective treatment for end-stage heart failure, yet fewer than half of donor hearts are ultimately used. One major reason is the relatively short window for transplanting a donated heart into a patient, due to concerns over low donor heart function that comes from leaving a heart in cold storage too long.  

Why donor hearts deteriorate in cold storage

Although cold storage slows metabolism and helps preserve tissue, prolonged exposure to cold storage conditions can lead to molecular changes that compromise how well the heart performs after transplant. One complication is called primary graft dysfunction, in which the transplanted heart cannot pump blood effectively after surgery. This may affect up to 20% of recipients to varying degrees.

To investigate why this damage occurs, the researchers focused on a protein inside heart cells called the mineralocorticoid receptor, which plays a role in how cells respond to stress. During cold storage, they found that this protein undergoes a process in which the protein clumps together in a way that harms the heart cells, called liquid-liquid phase separation. This process promotes cardiac damage from increased inflammation and cell death, making the heart less likely to function well after transplant.

Preventing damage with a common drug

To test whether the process could be prevented, the researchers treated donor hearts with a drug called canrenone, which blocks mineralocorticoid receptor activity. In human donor hearts stored beyond the typical timeframe, treatment with the drug nearly tripled their pumping strength compared to hearts stored without it. The hearts also showed better blood flow and fewer signs of cell injury. The findings suggest canrenone may help extend the safe storage period for donor hearts by improving the heart’s pumping strength to increase chances of a successful transplant.

"As a cardiovascular surgeon, I’ve personally experienced in the operating room how every additional hour of preservation can impact the likelihood of whether a donor heart can return to normal function after transplantation," Dr. Tang says. "This discovery may give us a new tool to preserve heart function for longer during storage, improve transplant outcomes and enhance patient access to lifesaving transplants."

The study's findings also have the potential to improve the preservation of other transplantable organs. Similar protein clustering was observed in donor kidneys, lungs and livers during cold storage. This suggests that the same strategy may help expand transplant options across multiple organ systems.

Mayo Clinic collaborated with the University of Michigan on this research. Review the study for a complete list of authors, disclosures and funding. 

### 

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:  

• Susan Murphy, Mayo Clinic Communications, newsbureau@mayo.edu 

The post Mayo Clinic discovery could mean better access to more donor hearts and improved transplant outcomes appeared first on Mayo Clinic News Network.

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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José Villalta prided himself on providing for his wife and son, first by working construction jobs and then by canning vegetables at Faribault Foods. He was known for being strong and capable, with dark eyes and an easy smile. But in his early 40s that changed, and quickly. "I don't feel the same," he told his wife, Sylvie. His muscles, once one of his defining features, grew progressively weaker. He had trouble walking. Within months, he had to use a cane, then a wheelchair, to get around.

Doctors told him to take more vitamins. They tried acupuncture and electroshock therapy. A specialist biopsied a piece of his leg muscle but could not determine the cause of his deteriorating health. By the time he made his way to Mayo Clinic, he could no longer muster the strength to lift his arms or even hold up his head. "He was like a puppet," says Sylvie.

Ashley Santilli, M.D., the clinical fellow at Mayo Clinic assigned to his case, told the family not to lose hope. "She was really persistent," recalls Sylvie. "She said 'We will get to the bottom of this — we will figure out what's wrong.'"

Integrated know-how

At the time, Dr. Santilli was training under Teerin Liewluck, M.D., a neurologist who had trained under the late Andrew Engel, M.D., a pioneer of muscle disease research. Over nearly six decades at Mayo Clinic, Dr. Engel discovered several new neuromuscular disorders and identified the underlying mechanisms of many others.

"One thing he always told me was that he was still learning, even after all those years," says Dr. Liewluck. "He taught me that I need to keep an open mind, because there's always new things to learn and discover."

Because Villalta's mysterious illness arose rapidly and later in life, Dr. Liewluck thought the cause was probably not genetic. Congenital muscle diseases typically emerge slowly in early childhood. But when he looked at Villalta's muscle biopsy under the microscope, he was surprised to see abnormally large mitochondria, the energy-producing structures often called the "powerhouses of the cell." Giant mitochondria (also known as megaconia) are associated with a type of congenital muscular dystrophy caused by mutations in a gene called CHKB.

To make sure they were not missing a new presentation of this incurable condition, the team requested genetic testing, which confirmed that Villalta did not harbor any suspicious CHKB variants. So they returned to the biopsy in search of more clues.

"The unique thing about neuromuscular medicine at Mayo is we get specific training in diagnostic tests, like biopsy interpretation and EMG," says Dr. Santilli, referring to electromyography, a test that measures muscle response to nerve stimulation. "You get to be the whole provider for a particular patient, instead of relying on other specialists to help us interpret those tests."

A new disease

Villalta's case gave Dr. Liewluck a sense of déjà vu. He recalled another patient, years earlier, who was part of a study on a severe form of muscle inflammation. That patient's biopsy also was marked by giant mitochondria. The patient's story was only pieced together later: an adult who developed muscle weakness, but whose illness was complicated by an underlying cancer. Treated by another physician, the patient initially improved with immunotherapy, but ultimately the cancer claimed her life.

To better understand Villalta's muscle disease, the researchers performed a series of special stains on his biopsy, each revealing various aspects of muscle structure and pathology. In addition to the unusually large mitochondria within his muscle fibers, they found evidence of inflammation, indicating an autoimmune process was at play. The team believed that Villalta's immune system was mistakenly attacking his muscles. If they were right, then immunotherapy might help him regain his strength.

"We couldn't guarantee or predict the outcome," says Dr. Liewluck.

They told Villalta that he would be the first patient they treated with this new disease, which they called immune-mediated megaconial myopathy (IMMM). They treated him aggressively with regular rounds of intravenous immunoglobulin and steroids. And he got better.

Before treatment, Villalta's levels of creatine kinase, a blood biomarker commonly used to monitor muscle damage, were sky high. With treatment, those levels dropped back within the normal range, suggesting that his overactive immune system had been put in check. More importantly, Villalta felt stronger and required less assistance, showering on his own, tinkering in his garage — even driving himself to rehab.

Unfortunately, Villalta's illness may have gone too long without treatment to allow a full recovery. Chronic inflammation and repeated muscle damage can gradually lead to the replacement of healthy muscle tissue with fat and scar tissue.

"That gives you evidence that you need to catch these cases earlier," says Dr. Liewluck.

Earlier answers

The team turned to the Mayo Clinic Muscle Pathology database to see if they could find other patients with this new disease within recent years. They identified two more patients, who shared the same distinctive features — profound muscle weakness in adulthood, strikingly enlarged mitochondria, inflammatory reaction in muscle tissue and elevated creatine kinase levels. Working in collaboration with an outside institute, they uncovered a third case. Along with Villalta and the case from the prior research study, the count had risen to five. Villalta and the two newer patients, all of whom received immunotherapy, responded well to treatment.

Now, Dr. Liewluck is delving deep into Mayo Clinic's extensive muscle tissue repository, combing through biopsies that span not just recent years, but decades, in search of other overlooked cases — patients who may have had IMMM long before it was recognized as a distinct entity.

"I actually think there might be many more than we know," says Dr. Santilli.

Interestingly, all the patients they have identified thus far have also had some form of pancreatic disease, such as pancreatic cancer or pancreatitis. Though the link is not entirely clear, the pancreas expresses high levels of choline kinase beta, the same protein that is disrupted in CHKB-related muscular dystrophy. Dr. Liewluck is collaborating with neuroimmunologist Div Dubey, M.B.B.S., to try to identify the antibody that triggers the immune attack, ultimately causing disease.

Once they find that autoantibody, they can test for it in the blood to diagnose more patients with IMMM. For now, they will have to rely on their expert review of muscle biopsies combined with clinical observations.

Though Villalta is not back to his old self, he is happy that his case has already helped others. And he is making the most of the strength he has.

By last spring, Villalta had recovered enough to travel to his home country of El Salvador. His family helped him take a walk on the beach and watched over him as he swam in the ocean. Until recently, it was more than he thought was possible.

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