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.

ROCHESTER, Minn. — Photon therapy offers strong outcomes in treating oropharyngeal cancers; however, some radiation can reach and damage nearby healthy tissue. The damage can lead to side effects that may be severe for some patients. In a new nationwide study published in The Lancet that included Mayo Clinic, investigators found that patients with oropharyngeal cancer can live longer with fewer side effects if treated with proton beam radiation therapy.

Photon radiation therapy, which uses X-rays to cure cancers, is a standard treatment for a type of throat cancer called oropharyngeal cancer. Rates of oropharyngeal cancers are increasing in the U.S., mainly driven by HPV infection.

Reducing the toll of treatment 

Proton beam therapy has been used for years in children, where research shows it lowers both short- and long-term treatment-related side effects. "Protons have been studied extensively in pediatric populations and consistently demonstrate reduced short- and long-term toxicity," says Nadia Laack, M.D., chair of the Department of Radiation Oncology at Mayo Clinic in Rochester. "It has been more difficult to prove the benefits in adult cancer because many adult studies have not measured side effects as carefully or as long." 

To explore whether the same advantages apply to adults, investigators directly compared proton beam therapy with modern photon radiation called intensity-modulated radiation therapy (IMRT), which precisely targets tumors while limiting exposure to nearby healthy tissue. "It is effective as an oropharyngeal cancer treatment, but there's always some incidental dose to surrounding tissues because of the physical nature of X-rays," says Daniel Ma, M.D., radiation oncologist at Mayo Clinic and the Mayo site primary investigator of the study. This incidental dose of radiation can sometimes cause long-term complications, including pain, problems with swallowing and a weakened jawbone.

To alleviate these unwanted side effects, investigators studied proton beam radiation therapy as a treatment option. "Protons are charged particles that can stop at a certain depth, so the delivery is more focused," says Dr. Ma. "If you set up your proton fields thoughtfully, you can avoid irradiating critical structures like the mouth, voice box and swallowing muscles. That's the advantage of proton therapy and why we decided to investigate it within a clinical trial."

Mayo Clinic was one of 18 participating institutions around the U.S. that enrolled patients in the first-ever phase 3 randomized trial comparing the two types of radiation for oropharyngeal cancer. Dr. Ma collaborated with Robert Foote, M.D., emeritus professor of radiation oncology at Mayo Clinic and senior author of the study, and Samir Patel, M.D., radiation oncologist at Mayo Clinic, to help lead Mayo Clinic’s involvement in the study.

Study results found that proton beam therapy weakened the immune system by 15% less than photon therapy. It also lowered the risk of severe swallowing problems by 13% and reduced the need for feeding tubes by more than 13%.

An unexpected outcome 

The treatments were similar in effectiveness in controlling cancer growth and spread, so Dr. Ma expected survival to be approximately the same, but the survival results were surprising.  

"Unexpectedly, we found that the overall survival at five years was 91% with proton therapy and 81% with photon therapy," he says. 

These results weren't immediately apparent. "The survival benefit in our study didn't start separating out until three years and wasn't apparent until five years, so longer follow-up with patients was key," he says. 

Dr. Ma says this result is likely due to a variety of factors, including less toxicity and immune suppression. He adds, "Because of this, we feel strongly that proton therapy should be a standard treatment for oropharyngeal cancer patients who can tolerate and receive it." 

"This study is important because it confirms what we believe to be true in many adult cancer cases: reducing toxicity has a meaningful impact on quality of life and long-term outcomes," says Dr. Laack. "As our treatments improve and our patients live longer, reducing toxicity and improving quality of life is more important than ever." 

The study was led by The University of Texas MD Anderson Cancer Center. Review the study 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. 

Media contact: 

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

The post Joint study finds proton beam therapy helps patients with throat cancer live longer with fewer side effects  appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Clinicians typically classify meningiomas — the most common type of brain tumor — into three grades, ranging from slow-growing to aggressive.

But a new multi-institutional study suggests that appearances may be deceiving. If a tumor shows activity in a gene called telomerase reverse transcriptase (TERT), it tends to recur more quickly, even if it looks low-grade under the microscope.

The findings, published in Lancet Oncology, could significantly change how doctors diagnose and treat meningiomas.

"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."

This research was presented at the Society for Neuro-Oncology conference on Nov. 22.

"This is one example of how precision diagnostics of cancer may ultimately improve patient outcomes," says Kenneth Aldape, M.D., Mayo Clinic pathologist and study co-author.

An early warning sign

Meningiomas — tumors of the meninges, the protective tissue that surrounds the brain and spinal cord — are generally considered benign. But a small subset of these tumors has a mutation in the TERT gene, which is linked to faster growth and a shorter time before the tumor returns after treatment.

TERT is the active part of telomerase, an enzyme that maintains telomeres, the protective ends of chromosomes. In most healthy adult cells, TERT is switched off. But if it becomes switched back on, it can fuel cancer development by driving unchecked cell growth.

In this study, the researchers wanted to see whether high TERT expression, even in the absence of the TERT genetic mutation, also predicted worse outcomes. They looked at more than 1,200 meningiomas from patients across Canada, Germany and the U.S., and they found that nearly one-third of them had high TERT expression despite not having the mutation.

These patients had earlier tumor regrowth compared to those without TERT expression, though their outcomes were better than patients with full-blown TERT mutations.

"TERT-positive tumors behaved like they were one grade worse than their official diagnosis," says Dr. Zadeh. "For example, a grade 1 tumor with TERT expression acted more like a grade 2."

Guiding treatment decisions

The findings suggest that testing for TERT activity could help doctors predict which patients are at higher risk for recurrence and may need closer monitoring or more intensive treatment.

"Because meningiomas are the most common primary brain tumor, this biomarker could influence how thousands of patients are diagnosed and managed worldwide," says Dr. Zadeh.

"TERT expression can help us more accurately identify patients with aggressive meningiomas," Chloe Gui, M.D., a neurosurgery resident at the University of Toronto, Mayo Clinic research collaborator and the study's lead author, explains on a podcast hosted by The Lancet Oncology. "This information allows us to offer treatment tailored to the tumor's behavior."

The team is currently investigating ways to incorporate TERT expression into the clinical workflow. The research is part of a larger effort at Mayo Clinic called the Precure initiative, focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

Review the study 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 to 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 New genetic biomarker flags aggressive brain tumors appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have identified a specific immune cell that can be targeted to give a boost to standard immunotherapies for cancer. Two research teams, working collaboratively but using distinct approaches, found that "first-responder" immune cells known as myeloid cells can be manipulated to enhance the activity of tumor-killing T cells.

The finding suggests that enhanced myeloid cells may boost certain immune checkpoint therapies, which are the standard of care for some cancers but may not have lasting effects. A clinical trial is now being developed at Mayo Clinic to test the enhanced cells in patients.

In a study in Journal for ImmunoTherapy of Cancer, Mayo Clinic researchers detailed how they found a way to boost cancer-killing T cells. The goal was to improve treatments that interfere with immunosuppressive proteins, PD-1 and PD-L1, which together suppress T cells' ability to fight cancer. Even though PD-L1 immunotherapies aim to block PD-L1, the researchers found that the molecule can persist through a natural recycling process that puts it back in play.

"Our study found the importance of the recycling process, and we present a way to address it," says Haidong Dong, M.D., Ph.D., a cancer immunology researcher at Mayo Clinic Comprehensive Cancer Center and principal investigator of the study.

The research team developed an antibody, H1A, which they found can reduce PD-L1 in human myeloid cells and keep it from recycling. The protein PD-L1 is present in abundance on the surface of myeloid cells. When the protein was prevented from recycling on myeloid cells, the cells then boosted the action of cancer-killing T cells.

"We now have a tool that can completely remove PD-L1 and in doing so we have more myeloid cell activation," says lead author of the study, Michelle Hsu, who conducted the research as her graduate thesis at Mayo Clinic Graduate School of Biomedical Sciences. "Identifying the myeloid cell was an unexpected discovery," she says.

Another Mayo Clinic team took a different approach and arrived at a similar conclusion about the importance of myeloid cells. A research team led by immunology researcher Jessica Lancaster, Ph.D., at Mayo Clinic in Arizona, reported in iScience that macrophages, a type of myeloid cell, play a role in activating the cancer-killing T cells.

Watch animation

Animation available in the downloads: Live cell microscopy shows a cancer-killing T cell (magenta) as it migrates and interacts with macrophages (blue) in the tumor microenvironment. Black spaces are packed with non-fluorescent tumor cells. Image captured by Tina Kwok, Mayo Clinic.

Using the complex approach of live-cell microscopy, the team found that in mice, T cells interact closely with the macrophages and create a molecular environment that has greater capacity to kill a tumor.

"This is a paradigm shift for PD-L1 immunotherapy, which has traditionally focused on the interaction of the tumor and the T cells," says Dr. Lancaster. "We found that it’s important to co-opt the macrophage, which acts as another immune cell partner."

Further, says lead author Tina Kwok, who completed the studies during her Ph.D. research at Mayo Clinic, "We can directly reprogram tumor macrophages to be more pro-inflammatory. They can become better T-cell activators and drive better tumor control. Reprogramming of the macrophage may be key to being able to prevent therapy resistance and change outcomes for patients."

Based on the findings from both labs, a phase 1 clinical trial of H1A is being planned. The research could ultimately better address resistance to immunotherapy and expand treatment options for people with cancer.

Review the studies in Journal for ImmunoTherapy of Cancer and iScience for a complete list of authors, disclosures and funding.

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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.

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

Media contact:

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

The post Mayo Clinic researchers find enhancing the body’s ‘first responder’ cells may boost immune therapy for cancer appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have discovered a key reason why certain breast cancers might not respond to an important new class of therapeutics called antibody drug conjugates (ADCs). These treatments pair an antibody that targets cancer cells with a strong chemotherapy drug. For many patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancers, ADCs such as trastuzumab deruxtecan (T-DXd) have dramatically improved outcomes.

"While T-DXd has shown remarkable results for many patients, it hasn't worked for everyone with advanced HER2+ breast cancer," says Peter Lucas, M.D., Ph.D., vice chair for research in the Department of Laboratory Medicine and Pathology at Mayo Clinic and co-senior author of the study, published in Nature Cancer. "This indicates that some tumors have built-in resistant mechanisms that prevent the drug from doing its job."

In the study, researchers in the Oncoimmune Signaling and Therapeutics Laboratory at Mayo Clinic discovered that a shortened version of the HER2 protein, called p95HER2, that is produced by a subset of HER2+ breast cancers can alter treatment response. The protein p95HER2 "signals differently" from the full HER2 oncoprotein — which proved to be the key to how it drives therapy resistance.

"Our discovery that p95HER2 has the unique ability to induce signals that produce an immune-protected microenvironment strongly suggested that p95HER2 could function within cancer cells to actively resist T-DXd," says Dr. Lucas.

The study also revealed that a drug called neratinib is highly effective at blocking the action of p95HER2, even causing the protein to be degraded.

"In fact, treatment with neratinib results in complete p95HER2 degradation, abolishing the protein from the cancer cells in our preclinical models," says Dong Hu, Ph.D., a research scientist in Laboratory Medicine and Pathology at Mayo Clinic and lead author of the manuscript.

Based on these findings, the research team believes the next step is a clinical trial to evaluate the combination of neratinib with T-DXd in patients with HER2+ early breast cancer. The goal is to determine if this combination therapy can improve the response in cancers that co-express p95HER2 along with full HER2.

They note that this is just one of many therapeutic combinations being considered.

"No single, one-size-fits-all approach to treatment will work for every patient with HER2+ breast cancer," says Linda McAllister, M.D., Ph.D., a pediatric hematologist/oncologist at Mayo Clinic and co-senior author of the study.

However, with the discovery of p95HER2's role, a clear roadmap for future treatment is in sight.

"Having this new understanding of why T-DXd does not always work helps us to envision next steps toward customized therapies and more cures," says Dr. Lucas. "It's all about staying one step ahead of cancer."

For a complete list of authors, disclosures and findings, review the study. The work was supported by the Mayo Clinic Breast Cancer SPORE.

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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.

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

Media contact: 

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

The post Mayo Clinic discovery of breast cancer treatment resistance can lead to new hope for some appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A genomic test co-developed by Mayo Clinic and SkylineDx can identify whether people with melanoma are at low or high risk for cancer in their lymph nodes — a finding that could guide treatment decisions and help some people avoid lymph node biopsy surgery. The study results are published in JAMA Surgery.

In the largest prospective study of its kind, about 93% of people classified as low risk had no cancer in their lymph nodes, while about 25% in the high-risk group did. The multicenter clinical trial enrolled 1,761 people with early- or intermediate-stage melanoma at nine U.S. cancer centers between 2021 and 2024. 

Decoding the tumor’s genomic blueprint

The test measures the activity of eight genes in a melanoma tumor and combines that data with a person's age and tumor thickness to estimate the chance that cancer has reached the lymph nodes. The Merlin CP-GEP Test analyzes tissue from the tumor already collected during an initial biopsy, so no additional procedure or visit is required for the test.

Sentinel lymph node biopsy is performed under anesthesia to remove one or a few lymph nodes and check for microscopic cancer. The procedure usually requires a second incision and can have side effects, yet nearly 80% of people who undergo the surgery have no cancer in their lymph nodes.

"Surgery will always be central to cancer care, but this study shows that sentinel lymph node surgery might be avoided for selected patients with melanoma," says first author Tina Hieken, M.D., a surgical oncologist at the Mayo Clinic Comprehensive Cancer Center and co-principal investigator of the study. "This test lets us use a patient's own tumor biology to guide care with true precision."

Turning molecular insight into clinical impact

Melanoma is the deadliest form of skin cancer. While early-stage disease can often be treated successfully, once melanoma spreads to the lymph nodes, the risk of recurrence increases. Determining whether the cancer has reached the lymph nodes is a key step in guiding treatment.

"Melanoma progression is driven by subtle molecular processes that we're only beginning to understand," says Alexander Meves, M.D., a dermatologist at the Mayo Clinic Comprehensive Cancer Center who led earlier validation studies of the test. "This work translates that biology into tools that can improve care."

Researchers are now studying how incorporating the test into melanoma care might help healthcare professionals understand the risk of recurrence and guide follow-up care.

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

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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.

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 New genomic test could spare some people with melanoma from lymph node biopsy surgery  appeared first on Mayo Clinic News Network.

JACKSONVILLE, Fla. — About 50% of menopausal women experience genitourinary syndrome of menopause (GSM) that involves changes to the genitals, including the vagina, urethra and bladder. When estrogen levels drop during menopause, it can cause the GSM symptoms of vaginal dryness, itching, burning, frequent urinary tract infections and pain during sex. Replenishing the hormone through vaginal estrogen is an effective GSM treatment. But many breast cancer survivors either can't or don't want to use estrogen.  

More than 4 million people in the U.S. are breast cancer survivors. GSM affects up to 70% of these survivors. Medications that stop the body from producing estrogen can prevent or stop the spread of breast cancer. However, these antiestrogen therapies, called aromatase inhibitors, also can exacerbate GSM symptoms. 

"Our data shows that as many as 20% of breast cancer survivors on aromatase inhibitors will stop taking their medication prematurely because they cause severe GSM symptoms. This early discontinuation of their breast cancer therapy can lead to worse outcomes in breast cancer survivorship. So, clearly, nonhormonal treatment options for GSM are needed," says Anita Chen, M.D., a gynecologist at Mayo Clinic in Florida. Dr. Chen is the lead author of a study published in Obstetrics & Gynecology.  
 
This need drove Dr. Chen to search for another option. Her team conducted a phase 1 clinical trial with 20 breast cancer survivors with GSM to test the efficacy of platelet-rich plasma (PRP), the part of the blood that holds healing properties, to see if it could help. Blood was drawn from each participant and then spun in a centrifuge to obtain platelets and plasma that have self-healing and regenerative effects. PRP was then injected diffusely once into the opening of the vagina and the vaginal canal in each participant. 

"After six months, the breast cancer patients' GSM symptoms had significantly improved, including sexual function, urinary symptoms and overall quality of life, even amongst those taking estrogen blockers," says Emanuel Trabuco, M.D., a Mayo Clinic researcher and co-author of the study. 

While vasomotor symptoms of menopause, such as hot flashes and night sweats, can improve over time, GSM does not improve without treatment and worsens over time.  

"All of our participants completed the injection protocol and rigorous follow-up, which suggests that this population desires treatment for a bothersome condition, one that is likely underreported, underestimated and undertreated," says Dr. Chen. "Most importantly, none of the participants stopped their breast cancer treatment or experienced cancer recurrence during the study." 

PRP has been used for years in orthopedics and dermatology, and gynecologists have started looking into it to treat stress urinary incontinence, reproductive medicine and GSM. 

The next step in this research includes pursuing a phase 2 randomized controlled clinical trial to compare PRP injection with a placebo to treat GSM in breast cancer survivors and further evaluate its efficacy. 

Review the study 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. 

Media contact: 

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

The post Breast cancer survivors find relief for debilitating menopause symptom appeared first on Mayo Clinic News Network.

Radiation therapy is a common component of breast cancer treatment for patients. The high-powered beams of intense energy kill cancer cells and reduce the risk of the cancer recurring.

Dr. Laura Vallow, chair of the Radiation Oncology Department at Mayo Clinic in Florida, explains how innovation is transforming radiation treatments.

Watch: The Mayo Clinic Minute

Journalists: Broadcast-quality video pkg (1:05) is in the downloads at the end of the post. Please courtesy: "Mayo Clinic News Network." Read the script.

Patients with breast cancer now have more options when it comes to radiation treatments. The goal is to remove any remaining cancer cells following chemotherapy or surgery. 

"In other situations, we use radiation if the cancer is more advanced, or spread to the lymph nodes," says Dr. Vallow.

Advancements in technology allow healthcare professionals to treat patients more safely. One technique called "prone positioning" reduces the chance of beams targeting other organs. For this procedure, patients lie on their stomachs.

"We take advantage of gravity, the breast pulls away from the body, and we can treat the breast without exposing the underlying lung and heart to unnecessary radiation," explains Dr. Vallow.

Intensity-modulated radiation therapy is cutting-edge. Unlike traditional radiation, this procedure delivers X-rays directly to the targeted area from multiple angles, allowing for higher, more effective doses.

"Before intensity-modulated radiation therapy, we were not able to conform the dose around the chest wall," says Dr. Vallow.

For patients undergoing radiation therapy, it's crucial to stay hydrated and try to sleep well to fight fatigue. It's also important to use sunscreen after treatment.

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• Mayo Clinic treats first person in the US with a novel radiopharmaceutical therapy for breast cancer
• Mayo Clinic Minute: MRI for dense breasts — what to know
• Mayo Clinic Q&A: How to decide which breast cancer surgery is right for you
• (VIDEO) Back on the bench: Judge’s metastatic breast cancer journey inspires hope
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The post Mayo Clinic Minute: Radiation therapy for patients with breast cancer appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have identified a protein that acts like a traffic controller for DNA, preventing damage during cell division — a discovery that could lead to new cancer therapies, according to a study published in Nature.

"DNA is the code of life. It's critical for how a cell functions, but it's also critical for our own being and defines what we are," says Zhenkun Lou, Ph.D., the Swanson/Schmucker Endowed Professor to Support Health and Cancer Research at Mayo Clinic and the senior author of the new study.

When cells divide, DNA must be copied from one cell to the next — a process called replication. Dr. Lou's research team discovered that a protein called KCTD10 plays a surprising role in protecting DNA during this critical stage. Acting like a built-in sensor, KCTD10 helps shield the DNA replication machinery from damage. 

Cells also depend on another key process called transcription, where the cell decodes the DNA to create RNA. That RNA then can be translated into proteins, which are essential for healthy tissues and the body's everyday functions.

The problem is that the different machines that run these two processes — replication and transcription — travel on the same strand of DNA, like a narrow highway. The replication machinery moves faster than the transcription machinery. Therefore, collisions resulting in DNA damage inevitably occur. Researchers did not know how cells communicate to prevent or recover from these collisions until now.

Dr. Lou's research team saw that KCTD10 can sense when a collision is about to occur and act like a traffic controller, triggering a series of responses to prevent it. The protein activates an enzyme called CUL3 that steps in to tell the slower transcription machinery to move aside and allow the replication machinery to pass, avoiding harmful breaks to the DNA. CUL3 and KCTD10 achieve this through a process called ubiquitination that removes the proteins in front of the replication machinery.

It has long been observed that DNA replication and transcription run in the same direction. The findings in this study suggest that KCTD10 may play a significant part in this, shaping the overall organization of the human genome.

Killing cancer cells

"I became interested in the idea that if we can better understand how these processes normally occur, then we can more effectively target cancer cells where these processes malfunction, tipping them over the edge towards cell death," says Jake Kloeber, an M.D.-Ph.D. student and co-lead author of the study. He conducted the study in the Ph.D. component of his dual degree at Mayo Clinic Graduate School of Biomedical Sciences and Mayo Clinic Alix School of Medicine. Kloeber plans to pursue a career as a physician-scientist in radiation oncology.

When KCTD10 is missing, it leads to genomic instability and mutations that can result in tumor formation. Previous research has also shown that developmental delays are linked to the loss of KCTD10.

On the other hand, in cancer cells that lack the protection of KCTD10 because the replication and transcription machinery do not work properly, the missing protein can serve as a biomarker for the vulnerability of these cancer cells.

"We can take advantage of that and attack those cancer cells when they are most vulnerable, which opens a new therapeutic window for us to treat certain types of cancer," says Dr. Lou.

Next steps in this research are identifying which types of cancer are missing this protein and pinpointing ways to target those cancer cells with new or existing cancer drugs. 

The research is part of a larger effort at Mayo Clinic called the Precure initiative focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

Review the study 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.

Media contact:

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

The post Mayo Clinic researchers discover ‘traffic controller’ protein that protects DNA, and may help kill cancer cells appeared first on Mayo Clinic News Network.

Researchers are leading the nation in developing powerful and precise radiopharmaceutical theranostics intended to treat people with deadly cancers.  

ROCHESTER, Minn. — Mayo Clinic recently became the first institution to administer an investigational radioactive medicine to a patient with hepatocellular carcinoma (HCC), the most common type of liver cancer. The investigational medicine is a targeted radiopharmaceutical theranostic (RPT) that is designed to target a novel protein called glypican-3 (GPC3). The RPT was administered to the patient as part of a first-in-human clinical trial for the targeted therapy. This investigational RPT includes both a diagnostic imaging agent, intended to identify the cancer cells, and a therapeutic agent, intended to target and kill cancer cells.

GPC3 was identified as a potentially viable and promising target because it is produced at higher levels in HCC tissue than in a normal, healthy adult liver. It is also considered an oncofetal cell surface protein because GPC3 is normally only active during fetal development. In adults, the protein is turned off, but when cancer forms, it "reawakens" the protein to support rapid growth and evade the immune system. This means that GPC3 is found only on cancer cells, which makes it a strong potential target for treatment.  

With this knowledge, Mayo Clinic researchers are participating in a first-in-human clinical trial investigating alpha-emitting RPTs, which use alpha particle radiation to precisely and powerfully diagnose, target, and potentially kill cancer cells. In this trial, the RPT includes an agent that binds to GPC3.

The phase 1/1b study is being conducted at all three academic Mayo Clinic sites in Rochester; Phoenix; and Jacksonville, Florida. The first person to receive the clinical trial procedure was at Mayo Clinic in Florida.

"Whole-body GPC3 targeted molecular imaging shows high localization to the tumor and minimal accumulation in normal tissues, indicating that the therapeutic radiation effects will be limited to sites of disease," says Ephraim Parent, M.D., Ph.D., a radiologist and division chair of Nuclear Medicine at Mayo Clinic in Florida. Dr. Parent is co-principal investigator on the trial.

Mayo Clinic in Florida researchers recently were the first in the U.S. to apply an investigational alpha-emitting radiopharmaceutical therapy in a treatment setting to a patient living with metastatic breast cancer. Mayo Clinic has now marked another remarkable first by delivering a different novel alpha-emitting investigational therapy to a patient with liver cancer, the second-leading cause of cancer-related deaths worldwide.

"At Mayo Clinic, we are committed to advancing innovative therapies that expand possibilities for those facing this devastating disease," says Lionel Kankeu Fonkoua, M.D., a medical oncologist at Mayo Clinic in Rochester and principal investigator of the trial. "Being able to offer access to this novel radiopharmaceutical approach reflects our dedication to pushing the boundaries of liver cancer care."

The drug for the study is being developed by RayzeBio Inc., a Bristol Myers Squibb Company, the sponsor of the active phase 1/1b clinical trial.

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Study Title: Study of the Theranostic Pair RYZ811 (Diagnostic) and RYZ801 (Therapeutic) to Identify and Treat Subjects with GPC3+ Unresectable HCC (GPC3)

• Descriptor: Study of the Theranostic Pair RYZ811 (diagnostic) and RYZ801 (therapeutic) to Identify and Treat Subjects with GPC3+ Unresectable HCC
• Principal Investigators: Principal investigators at Mayo Clinic are Lionel Kankeu Fonkoua, M.D.; Umair Majeed, M.B.B.S., M.D.; and Mitesh Borad, M.D. Co-principal investigators are Ephraim Parent, M.D., Ph.D.; Geoffrey Johnson, M.D., Ph.D.; and Felipe Martinez, M.D.
• Sponsor: RayzeBio Inc.
• Link: www.mayo.edu/research/clinical-trials/cls-20583570  

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:

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

The post Mayo Clinic uses investigational targeted radiopharmaceutical theranostic for hepatocellular carcinoma in first-in-human clinical trial appeared first on Mayo Clinic News Network.