Mayo Clinic researchers have identified a potential new way to monitor the progression of high-grade gliomas, one of the most aggressive types of brain cancer. Their feasibility study suggests that a personalized blood test tailored to each patient's tumor DNA could provide a faster and less invasive way to determine if the cancer is advancing. 

Currently, clinicians rely on scans and surgical biopsies to monitor gliomas, but both methods have limitations. For example, scans often cannot distinguish tumor growth from treatment effects such as inflammation. Biopsies require invasive procedures, making them impractical for routine monitoring. 

This new approach, published in Clinical Cancer Research, may provide clinicians with another tool to monitor tumor changes over time and adjust treatment as needed. 

"This research builds on years of studying genetic rearrangements and gives us a deeper understanding of the molecular mechanisms driving gliomas."

George Vasmatzis, Ph.D.

Tracking DNA fragments of gliomas

The findings focus on tumor DNA fragments circulating in the blood. As gliomas grow, some glioma cells die, shedding pieces of their DNA into the bloodstream and leaving behind genetic markers that are unique to the tumor. 

However, gliomas release fewer DNA fragments into the blood compared to many other cancers. This is because of the blood-brain barrier, a natural brain defense that prevents many substances from leaving the brain.  

To overcome this limitation, researchers focused on DNA junctions, a type of tumor-specific DNA fragment that is present in higher quantities. By targeting these markers, researchers achieved greater sensitivity, enabling them to detect even the smallest signs of tumor progression. 

Unlike normal DNA, which follows a structured sequence, these DNA junctions form when the tumor's genetic material breaks and rearranges. The study found that these amplified DNA junctions, due to their higher numbers, may provide a clearer picture of disease progression. 

"This research builds on years of studying genetic rearrangements and gives us a deeper understanding of the molecular mechanisms driving gliomas," says George Vasmatzis, Ph.D., a lead author of the study and co-director of the Biomarker Discovery Program at Mayo Clinic's Center for Individualized Medicine and Mayo Clinic Comprehensive Cancer Center. "It offers new possibilities for patient-specific monitoring and targeted interventions." 

Detecting tumor DNA

In the study, researchers analyzed samples from patients with high-grade gliomas. They used whole genome sequencing to map each tumor's unique genetic blueprint and pinpointed patient-specific DNA junctions. Researchers then developed personalized blood tests to search for these genetic markers in plasma. 

"By tracking each tumor's distinct molecular signature, we're aiming to shift from a reactive approach to one that's far more proactive,"

Terry Burns, M.D., Ph.D.

The test detected tumor DNA in approximately 93% of the cases where these DNA junctions were present. In some patients, tumor DNA levels in the blood rose before MRI scans showed any changes — offering a potential early signal for disease progression.

Dr. Vasmatzis collaborated with Mayo Clinic neurosurgeon Terry Burns, M.D., Ph.D., bridging the gap between cutting-edge research and clinical practice. 

"By tracking each tumor's distinct molecular signature, we're aiming to shift from a reactive approach to one that's far more proactive," says Dr. Burns, a co-author of the study. "This research could lay the groundwork for tools that help clinicians make the most informed treatment decisions as early as possible." 

Future studies will evaluate how well blood-based tumor tracking correlates with glioma progression across a larger group of patients. 

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

The post Mayo Clinic researchers reveal personalized approach to brain cancer monitoring  appeared first on Mayo Clinic News Network.

Video: A healthy liver transitions to cirrhosis, illustrating a potential outcome of metabolic dysfunction-associated steatotic liver disease — formerly known as nonalcoholic fatty liver disease — which affects nearly one-third of the global population. Getty Images.

Researchers at Mayo Clinic's Center for Individualized Medicine have made a groundbreaking discovery: a rare genetic variant that can directly cause metabolic dysfunction-associated steatotic liver disease, formerly known as nonalcoholic fatty liver disease. It is one of the most common diseases in the world. 

Until now, scientists believed the disease resulted from a combination of genetic and environmental factors. This study, published in Hepatology, reveals that in some cases, a single inherited variant can be the primary driver.  

The researchers identified this variant in the MET gene, which regulates liver repair and fat metabolism. When the gene malfunctions, fat accumulates in liver cells and triggers inflammation. Over time, this leads to fibrosis and scarring, which stiffens the liver. In severe cases, the disease progresses to cirrhosis, resulting in irreversible liver damage or liver cancer. 

Metabolic dysfunction-associated steatotic liver disease affects about one-third of adults worldwide. Its advanced form, metabolic dysfunction-associated steatohepatitis, is expected to become the leading cause of cirrhosis and the reason for liver transplants in the coming years. 

"This discovery opens a window into how rare inherited genetic variants can drive common diseases," says Filippo Pinto e Vairo, M.D, Ph.D., a lead author and medical director of the Program for Rare and Undiagnosed Diseases at Mayo Clinic's Center for Individualized Medicine. "It provides new insights into this disease pathogenesis and potential therapeutic targets for future research."  

A hidden error in the genetic code 

The discovery emerged from the genomic data of a woman and her father with metabolic dysfunction-associated steatohepatitis. They had no history of diabetes or high cholesterol, two common risk factors for fat buildup in the liver.  

With no clear explanation, researchers examined the DNA from more than 20,000 genes to find answers. They found a small but potentially significant error in the MET gene. 

In collaboration with the Medical College of Wisconsin's John & Linda Mellowes Center for Genomic Sciences and Precision Medicine, led by Raul Urrutia, M.D., the scientists determined that the mutation disrupted a critical biological process. 

Genes are made up of chemical letters that provide instructions for the body's functions. In this case, a single swapped letter — among thousands — scrambled the message, preventing the liver from properly processing fat. This rare variant, found in the family, has not been reported in existing literature or public databases. 

"This study demonstrates that rare diseases are not rare but often hidden in the large pool of complex disorders, underscoring the immense power of individualized medicine in identifying them, and enabling the design of advanced diagnostics and targeted therapies," Dr. Urrutia says.  

Tracing the genetic variant impact

To explore the variant's broader impact, researchers turned to Mayo Clinic's Tapestry study, a large-scale exome sequencing effort aimed at uncovering genomic drivers of disease. The Tapestry study analyzed germline DNA from over 100,000 participants across the U.S., creating a comprehensive genomic data repository that supports research into both well-known and emerging health conditions.  

Among nearly 4,000 adult Tapestry participants with metabolic dysfunction-associated steatotic liver disease, about 1% carried rare, potentially causative variants in the same MET gene. Of these, nearly 18% had variants in the same critical region as the initial woman and her father, further supporting its role in liver disease.  

"This finding could potentially affect hundreds of thousands, if not millions, of people worldwide with or at risk for metabolic dysfunction-associated steatotic liver disease," says Konstantinos Lazaridis, M.D., a lead author and the Carlson and Nelson Endowed Executive Director for the Center for Individualized Medicine. 

Dr. Lazaridis emphasized the significance of this discovery as it relates to the Tapestry study's impactful contributions.  

"Once a pathogenic variant is discovered, interrogating our Tapestry data repository is giving us a clearer lens into the hidden layers of disease, and this discovery is one of the first to demonstrate its scientific significance," Dr. Lazaridis says. "This finding highlights the profound value of studying familial diseases and the merit of large-scale genomic datasets, which can reveal rare genetic variations with broader implications for population health." 

Advancing genomics to transform care

This discovery also reflects the importance of integrating genomics into clinical care at Mayo Clinic, where teams use advanced technologies to help solve complex medical mysteries.  

Since its launch in 2019, the Program for Rare and Undiagnosed Diseases has helped more than 3,200 patients with complex and serious conditions gain access to comprehensive genomic testing. It collaborates with nearly 300 clinicians from 14 divisions across the enterprise to bring precision diagnostics to patients with rare conditions, including rare liver diseases. 

Future studies will explore how this genomic discovery in metabolic dysfunction-associated steatotic liver disease can inform targeted treatments and improve disease management. 

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

The post Groundbreaking discovery links inherited mutation to fatty liver disease appeared first on Mayo Clinic News Network.

A new Mayo Clinic study finds that people with Tourette syndrome have about half as many of a specific type of brain cell that helps calm overactive movement signals as people without the condition. This deficit may be a key reason why their motor signals go unchecked, leading to the involuntary tics that define the disorder. 

Published in Biological Psychiatry, the study is the first to analyze individual brain cells from people with Tourette disorder. The findings also shed light on how different types of brain cells may interact in ways that contribute to the syndrome's symptoms. 

"This research may help lay the foundation for a new generation of treatments," says Alexej Abyzov, Ph.D., a genomic scientist in Mayo Clinic's Center for Individualized Medicine and a co-author of the study. "If we can understand how these brain cells are altered and how they interact, we may be able to intervene earlier and more precisely." 

Tourette disorder is a neurodevelopmental condition that typically begins in childhood. It causes repeated, involuntary movements and vocalizations such as eye blinking, throat clearing or facial grimacing. Nearly 1 in 162 children in the U.S. have Tourette syndrome, according to the Centers for Disease Control. While genetic studies have identified some risk genes, the biological mechanisms behind the condition have remained unclear. 

A close look at key brain cells

To better understand what's happening in the brain with Tourette syndrome, Dr. Abyzov and his team analyzed more than 43,000 individual cells from postmortem brain tissue of people with and without the condition.

They focused on the basal ganglia, a region of the brain that helps control movement and behavior. In each cell, they looked at how genes were working. They also analyzed how changes in the brain's gene-control systems might trigger stress and inflammation.

First, they found in people with Tourette syndrome a 50% reduction in interneurons. These brain cells help calm excess signals in the brain's movement circuits.

They also observed stress responses in two other brain cell types. Medium spiny neurons make up most of the cells in basal ganglia. They help send movement signals and showed reduced energy production. Microglia, the brain's immune cells, showed inflammation. The researchers found a close link between the two responses, suggesting the cells may interact in Tourette disorder.

"We're seeing different types of brain cells reacting to stress and possibly communicating with each other in ways that could be driving symptoms," says Yifan Wang, Ph.D., co-author of the study.  

The study points to changes in DNA regions that control when genes turn on and off as a possible cause of brain cell changes in Tourette disorder. 

"Tourette patients seem to have the same functional genes as everyone else but the coordination between them is broken," says Dr. Abyzov. 

Next, the researchers plan to study how these brain changes develop over time and look for genetic factors that may help explain the disorder. 

The researchers conducted the study in collaboration with the lab of Flora M. Vaccarino, M.D., at Yale University. For a complete list of authors, disclosures and funding, review the study. 

The post Mayo Clinic uncovers brain cell changes that could explain Tourette syndrome  appeared first on Mayo Clinic News Network.

When Vicki Tennant came to Mayo Clinic for answers about her heart condition, she never expected to be at the center of a medical breakthrough. But her case led Mayo Clinic researchers to identify a previously undetectable genetic phenomenon.

Most genetic diseases are linked to protein-coding regions, which is also where standard testing has been focused. The discovery based on Tennant's case, published in Circulation: Heart Failure, was that disease-causing variants can hide in areas of DNA that don't make proteins.

Specifically, a tiny glitch in one of these regions, combined with a known mutation, was enough to cause Tennant's disease. 

"The level of care and expertise at Mayo Clinic is something I've never experienced," Tennant says. "It’s amazing to think that what they found in me could change how doctors diagnose others."

A clue hidden in the heart

In her home state of Iowa, Tennant had been diagnosed with hypertrophic cardiomyopathy, a genetic condition that thickens the heart muscle and increases the risk of heart failure. But her case didn't follow the usual pattern.

She had an irregular heartbeat that required several procedures to restore a normal rhythm, and she had also had a stroke. Her cardiologist in Iowa referred her to Mayo Clinic for further evaluation.

At Mayo Clinic, what began as a closer look at Tennant’s heart tissue by cardiologist Jeffrey Geske, M.D., quickly gained momentum. Pathologist, Joseph Maleszewski, M.D., examined the biopsy and identified microscopic abnormalities that indicated the need for further investigation.

Around the same time, Tennant underwent a routine gallbladder surgery in Iowa. A liver biopsy performed during that procedure also revealed abnormalities, prompting Tennant to ask her Mayo team to review the findings. That request helped deepen the investigation into the underlying cause of her health issues.

When standard clinical genetic testing did not yield an answer, Dr. Geske asked Naveen Pereira, M.D., a cardiovascular genomicist, to take a closer look at Tennant's DNA. Dr. Pereira searched Tennant's genome for hidden patterns and anomalies.

He found that Tennant had one known disease-causing mutation in a gene responsible for producing an enzyme that prevents substances from accumulating in the cell. Normally, two mutations are needed to cause a genetic condition called mucopolysaccharidosis type IIIA. But something still didn't add up — besides having only one variant, Tennant lacked some of the typical symptoms of the disease.

Dr. Pereira conducted additional lab tests to check for signs of the condition in her cells, however, which led to confirming it as her diagnosis.

Mucopolysaccharidosis type IIIA usually appears in early childhood and causes progressive neurological decline. But Tennant, in her 40s, had no signs of neurological issues. In her, the condition showed up as heart disease — an unexpected and atypical presentation that added to the mystery.

A genetic mystery unfolds

With unanswered questions remaining, Dr. Pereira expanded the team, bringing in experts from Mayo Clinic's Center for Individualized Medicine: Filippo Pinto e Vairo, M.D., Ph.D., medical director of Mayo Clinic’s Program for Rare and Undiagnosed Diseases; Eric Klee, Ph.D., the Everett J. and Jane M. Hauck Midwest Associate Director of Research and Innovation; and Laura Lambert, Ph.D., director of the Functional Omics Resource Laboratory.

The team applied advanced sequencing and analysis methods to search beyond the usual areas of the genome. That's when they made another discovery.

"We found a variant in a stretch of DNA located between two genes — it's a region often missed by standard genetic testing because it doesn't code for proteins," says Dr. Pinto e Vairo. "Now we had to prove it was actually disrupting how the gene worked and contributing to the disease in our patient."

To validate the finding, Dr. Lambert and the Functional Omics Resource Laboratory team used innovative, light-based methods to test whether the DNA change was interfering with how the gene worked.

"This gave us the functional proof we needed to confirm that this variant was actually causing disease," Dr. Lambert says.

Combined with the known mutation previously identified by Dr. Pereira, this hidden change provided the missing explanation for Tennant's condition.

"This finding is a testament to the transformative potential of looking beyond the expected," Dr. Klee says. "It underscores how advancements in genomics and technology are enhancing our ability to understand the impact of an increasing number of genetic changes."

Together, these insights revealed an entirely new way genetic disease can emerge and take shape.

"This discovery highlights the strength of integrating advanced genomic science with clinical expertise to solve some of medicine's most complex mysteries," says Dr. Pereira. "This finding could help change our approach and diagnose other patients with unexplained conditions, and expand the scope of precision medicine."

A long-awaited answer

For Tennant, the discovery has provided long-sought clarity. She enjoys working on her farm, spending time outdoors and operating her tractor — all activities she now approaches with a deeper understanding of her health.

While there is no cure for Mucopolysaccharidosis type IIIA with cardiac involvement, her diagnosis allows for more precise monitoring and offers hope for potential future treatments, including gene therapy.

"I also hope this helps someone else," Tennant says. "If sharing my story means someone gets diagnosed sooner, then it's all worth it."

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

The post Hidden mutation leads to groundbreaking genetic discovery appeared first on Mayo Clinic News Network.

Every rare disease tells a story. Understanding how one unfolds — how it develops and evolves — is often the first step toward treating it. A small genetic error, a malfunctioning cell or a breakdown in a biological process can set disease in motion. But for many rare conditions, the course of progression remains unwritten. 

A groundbreaking natural history study led by researchers at Mayo Clinic's Center for Individualized Medicine and Department of Clinical Genomics aims to change that, advancing research for one rare disease with the potential to benefit many others. 

At the center of this effort is autosomal dominant leukodystrophy, a rare, hereditary neurodegenerative disorder. It is driven by a single genetic variant that causes an abnormal buildup of a protein. This disrupts nerve cell function and the brain's signaling network. Over time, this damage leads to a slow decline in movement, balance and essential body functions. 

A road map for research and treatment

This extensive study will track the disease from its earliest stages to advanced progression in patients from around the world. By analyzing patient medical records, brain imaging scans, genetic data, neurological assessments and more, researchers will develop a comprehensive dataset to identify key biological markers in people with the disease.  

These insights will serve as a foundation for future clinical trials. 

"Genetic therapies are increasingly becoming a reality for rare diseases, providing hope of a treatment that can address the root cause of the disease," says Margot Cousin, Ph.D., the study's lead investigator and director of the Center for Individualized Medicine's N-of-1 Therapeutics program. "We need to have systems in place to study these disorders so we can bring these therapies into clinical practice efficiently." 

"Genetic therapies are increasingly becoming a reality for rare diseases, providing hope of a treatment that can address the root cause of the disease."

mARGOT cOUSIN, pH.d.

What makes this disease so challenging?

Autosomal dominant leukodystrophy is classified as an ultra-rare disease, meaning it affects a small number of people worldwide. Fewer than 50 families have been identified, but researchers believe many cases go undiagnosed due to its similarities to other neurological conditions and limited access to genetic testing.  

Because it is so rare, most clinicians will never encounter a patient with autosomal dominant leukodystrophy (ADLD). When they do, the disease can be difficult to recognize, as its symptoms resemble other neurological disorders that affect the brain's protective nerve coating. This often leads to misdiagnosis and delays in care. 

Further, the type of genetic alteration that causes autosomal dominant leukodystrophy may not be detected using some common genetic testing methodologies, putting even more importance on the clinical recognition of the disease. Researchers emphasize the need to increase awareness of the disease among neurologists to help patients receive an accurate diagnosis sooner. 

How the study works

This natural history study is a collaboration with Children's Hospital of Philadelphia through the Global Leukodystrophy Initiative. This initiative has extensive expertise and infrastructure needed to capture and analyze data on autosomal dominant leukodystrophy at depth. 

Mayo Clinic researchers are working within this collaboration to improve how the disease is studied and to ensure data collection meets the highest clinical research standards.  

"We are creating a dedicated clinical and research infrastructure for identifying patients earlier so they can receive the highest level of multidisciplinary care."

Radhika Dhamija, M.B.B.S.

This study is also supported by the ADLD Center, a patient advocacy group, whose mission is to support research on the disease's pathology and therapy. The center provides patients, caregivers and families with essential resources and a strong support network.  

Improving diagnosis and clinical care

Alongside this natural history study, Mayo Clinic has established the Autosomal Dominant Leukodystrophy Clinical Care Center, dedicated to diagnosing and managing this disease. The center is led by Radhika Dhamija, M.B.B.S., a neurologist and medical geneticist in the Mayo Clinic Department of Clinical Genomics. This clinical care center coordinates care across neurology, urology, radiology, genomics and other specialties to provide the highest level of care for patients. 

"We are creating a dedicated clinical and research infrastructure for identifying patients earlier so they can receive the highest level of multidisciplinary care," says Dr. Dhamija. "This is about transforming the future of how we approach rare neurogenetic diseases." 

A model for future rare disease research

Mayo Clinic researchers see this natural history study on autosomal dominant leukodystrophy as a model for accelerating research in other ultra-rare conditions that remain understudied due to small patient populations. 

"We're building a framework that brings scientific clarity to diseases that have remained long overlooked," Dr. Cousin says.  

The post Mayo Clinic launches landmark study on rare neurological disease  appeared first on Mayo Clinic News Network.

(Video: Filippo Pinto e Vairo, M.D., Ph.D., medical director of Mayo Clinic’s Program for Rare and Undiagnosed Diseases, analyzes genetic data on screen, uncovering insights into rare disease.)

February 28 is Rare Disease Day, a time to recognize the millions of people worldwide living with conditions that often go undiagnosed or untreated. In the U.S., a disease is considered rare if it affects fewer than 200,000 people.

More than 7,000 rare diseases have been identified, many of them genetic. These conditions can affect vital organs, the nervous system, the immune system and other critical functions. 

At Mayo Clinic's Center for Individualized Medicine, researchers and clinicians are advancing precision medicine to improve diagnoses and develop treatments once thought impossible. A key part of this effort is the center's Rare Disease Omics strategy. This innovative approach moves discovery from the lab to patient care. 

By combining multiple layers of biological omics data, including genomics (study of genes), proteomics (study of proteins), and other molecular insights, scientists uncover how rare diseases form at their earliest stages and progress over time. Using omics tools, they identify mutations, examine disruptions in cellular function and trace how small errors in biological processes can lead to disease. 

"Our goal is to build a discovery pipeline," says Timothy Curry, M.D., Ph.D., the William O. Lund, Jr. and Natalie C. Lund Program Director for Clinomics, and the associate director of Practice Implementation at the Center for Individualized Medicine. Dr. Curry leads the center's Rare Disease Omics pillar.  

"Every breakthrough we make brings us closer to the day when rare diseases once thought untreatable can be managed or even cured," he says. 

Artificial Intelligence helps accelerate research

Artificial intelligence helps researchers identify genetic mutations and patterns that are difficult to detect through traditional methods. AI also helps teams search for existing drugs that might be repurposed for rare conditions.  

These advances are unlocking new treatment possibilities. Scientists are developing personalized therapies, including RNA-based treatments that target genetic errors without altering DNA. 

"Every breakthrough we make brings us closer to the day when rare diseases once thought untreatable can be managed or even cured."

Timothy curry, m.d. ph.d.

At the same time, Mayo Clinic is expanding efforts to provide answers for patients with unexplained conditions. The Program for Rare and Undiagnosed Diseases has delivered in-depth genomic analysis to more than 3,200 patients since its launch in 2019. 

Now, the next step is bringing these discoveries to more patients. Mayo Clinic is expanding genetic testing and counseling to give more people with complex conditions access to expert care and research.

Special presentations spotlight rare disease experts

To mark Rare Disease Day, Mayo Clinic will host a virtual event featuring a global leader in rare disease advocacy. 

February 27 at 12 p.m. CST – A Conversation with Dr. Durhane Wong-Rieger 

Durhane Wong-Rieger, Ph.D., president of the Canadian Organization for Rare Disorders and a key figure in the International Rare Diseases Research Consortium, will share insights on improving treatment access and driving innovation. She has been instrumental in shaping policies that expand options for patients. With expertise spanning global initiatives and groundbreaking research, she will discuss how advances in genomics and AI can bridge — or deepen — the divide in healthcare equity for rare disease patients worldwide. Learn more. 

Related story

Advancing rare disease breakthroughs with genomics, AI and innovation

Patient by patient, researchers at Mayo Clinic's Center for Individualized Medicine are making notable progress in rare disease diagnostics and treatments. Read more.

The post Mayo Clinic researchers blaze a trail of rare disease advancements appeared first on Mayo Clinic News Network.

In a study published in Science Advances, Mayo Clinic researchers found a new immunotherapy target called a cryptic antigen that may be key in helping the immune system fight tumors in ovarian cancer.

Cryptic antigens are part of a protein — known as epitopes — that are usually hidden or inaccessible to the immune system and may be present in tumor cells.

"These findings underscore the need to look at alternate sources of target antigens for ovarian cancer," says Marion R. Curtis, Ph.D., a Mayo Clinic senior associate consultant in immunology and senior author of the study.

Dr. Curtis explains that discovering tumor-associated antigens that T cells recognize is crucial for the success of immunotherapeutic approaches in ovarian cancer, where the growth of cells that form in the ovaries multiply quickly and can invade and destroy healthy body tissue.

T cells are a critical component of the adaptive immune system. Their ability to recognize and respond to specific targets is fundamental to their function. They play a significant role in developing and treating cancer and are vital in the immune system's fight against infections.

The researchers characterized the tumor antigens generated from ovarian cancer using multi-omics approaches to determine their ability to trigger an immune response. Multi-omics encompasses using multiple “omes” (i.e., genome, proteome, microbiome, epigenome) to better understand the mechanisms of disease processes, detection, potential prevention and more focused therapies.

Researchers have previously focused on discovering newly formed antigens (neoantigens). However, a previous study revealed that neoantigens are rarely found in ovarian cancer samples, making them unattractive targets. While targeted immunotherapies and immune checkpoint inhibitors have been highly successful in treating multiple cancer types, patients with ovarian cancer have limited benefit from these approaches.

What lies ahead?

Researchers will explore cryptic antigens in designing new treatments, such as vaccines or immunotherapies, that could help the immune system target tumors more effectively. They plan to test these approaches in laboratory models and clinical trials to see if they work safely.

The next steps include larger-scale studies to identify the abundance of cryptic antigen expression across different tumor types and to understand how those levels of cryptic antigens may correlate with patients' responses to immunotherapy.

Such studies could pave the way for developing immunotherapies targeting cryptic antigens in other tumor types. Moreover, understanding how cryptic antigens are processed and presented could offer new strategies to help the body's immune system fight cancer. In the long term, these efforts could broaden the reach of immunotherapy to other forms of cancer that currently lack effective treatment options.

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

The post Hope for ovarian cancer: New immunotherapy target appeared first on Mayo Clinic News Network.

Imagine knowing your risk for disease long before symptoms appear. With early detection and targeted interventions, this knowledge could transform how complex healthcare challenges are addressed. Researchers are now leveraging genetic data to enhance disease risk prediction through an innovative tool known as a polygenic risk score. Learn more on a new episode of Tomorrow's Cure.

The podcast's latest episode features Victor Ortega, M.D., Ph.D., associate director of the Mayo Clinic Center for Individualized Medicine, and Louise Wain, Ph.D., professor of respiratory research, University of Leicester in the U.K.

Scientists have developed polygenic risk scores to analyze multiple genetic variants across a person's genome. These scores assess the likelihood of developing conditions such as heart and lung diseases, diabetes, asthma, and certain cancers.

"There's really no one singular variant in the genome that causes common diseases. It's really a lot of different variants across the genome, across our genomes that have weaker or milder effects on disease risk, but all together give us this increased risk," explains Dr. Ortega.

"With those discoveries, we've developed genetic risk scores, polygenic risk scores, where we bring together the effects or associations across variants, across entire genomes into a singular score," he continues.

Clinicians can then utilize these risk scores to potentially customize prevention and treatment strategies.

"These are quite early in development, but are potentially really, really important," says Dr. Wain. "In the future, we could use these to improve diagnosis where somebody is already presenting with the disease, but they need a specific diagnosis in order to access the medicines that are going to work for them." Dr. Ortega says the potential of polygenic risk scores is both exciting and promising. Find out more on the latest episode of Tomorrow's Cure. To view the complete list of episodes and featured experts, visit tomorrowscure.com.

Related content:

• What's your health forecast? Expert explains science behind personal guides to well-being
• Mayo pioneers population science to advance personalized medicine

The post Tomorrow’s Cure: Predicting disease risk with polygenic risk scores appeared first on Mayo Clinic News Network.

Antibody-drug conjugates are targeted cancer therapies. They deliver potent drugs directly into cancer cells while minimizing harm to healthy tissue. These therapies work by recognizing specific proteins found on the surface of cancer cells.

The proteins function like a lock and the therapy acts as a key, latching onto the cancer cells with precision to deliver the treatment.

But precision alone isn’t enough. Even when the key fits the lock, the door often stays closed. This prevents the drug from entering the cell to attack the cancer. 

Now, Mayo Clinic researchers have developed a pioneering strategy that may help overcome this barrier. The approach combines antibody-drug conjugates with proteolysis-targeting chimeras. These molecular tools break down specific proteins to improve how cancer cells internalize the cancer-fighting therapy.  

"The ability to target specific proteins and improve drug absorption into tumor cells represents a significant step forward in how we approach aggressive cancers."

Aaron Mansfield, M.D.

In a preclinical study, published in Communications Biology, the combined therapy improved the internalization of these treatments by up to 1.9 times in certain models.  

"The ability to target specific proteins and improve drug absorption into tumor cells represents a significant step forward in how we approach aggressive cancers," says Aaron Mansfield, M.D., a medical oncologist and lead author of the study at the Center for Individualized Medicine and the Mayo Clinic Comprehensive Cancer Center. 

Dr. Mansfield and his team tested the approach using breast cancer organoids. They created these miniaturized, lab-grown versions of breast tissue to mimic the complexity of real tumors. Unlike traditional cell cultures, organoids better replicate how tumors behave in the body.

Specifically, the research focused on three proteins often found in aggressive cancers. These include human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and mesenchymal-epithelial transition factor (MET). These proteins are associated with breast, lung and pancreatic cancers.  

Overall, the study highlights the versatility of this approach by demonstrating potential benefits across multiple cancer types and protein targets. 

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

Other recent research from Dr. Mansfield

Innovative Mayo Clinic test may improve mesothelioma detection rate in blood

Dr. Mansfield and his team have developed an innovative testing strategy for mesothelioma that could potentially increase the detection rate of cancer DNA in the blood. Read more.

Researchers predict immunotherapy response in mesothelioma cancer

Dr. Mansfield and his team have discovered a potential genomic signature to predict which patients with mesothelioma could benefit from immunotherapy.  Read more.

The post Mayo Clinic opens new doors in cancer treatment innovation  appeared first on Mayo Clinic News Network.

Mayo Clinic researchers have developed organoid models to study uveal melanoma, one of the most common types of eye cancer in adults. Their goal is to use these models to better understand how this disease works and develop treatments for unmet patient needs.

Organoids are 3D models grown from patient tissue that accurately reflect a patient's unique genetic and biological characteristics, also known as "avatars." When derived from a patient's cancer tumor, an organoid will behave and respond to treatments outside the body in a lab (in vitro) just like the original tumor would inside the body (in vivo).

In 50% of patients, uveal melanoma metastasizes, spreading to other parts of the body, leading to a poor prognosis and average survival of less than two years.  Unfortunately, current treatments for this condition often have limited effectiveness, leaving patients and their doctors with few options.

"The hope is that these patient-derived organoid models better represent human cancer in the laboratory," says Lauren Dalvin, M.D., a Mayo Clinic Comprehensive Cancer Center ocular oncologist and surgeon-scientist who is one of the lead researchers. "Using these models as a foundation for drug testing will facilitate new treatment discoveries with higher success rates in clinical trials, ultimately translating to improved outcomes for patients with uveal melanoma."

Growing an eye cancer biobank

In the past, the lack of human disease models representing the entire spectrum of uveal melanoma has created a bottleneck, limiting the ability of scientists to identify effective targets for treatment and prevention. Most laboratory studies have drawn from the same set of commercially available cell lines, which are not representative of the disease and often differ in important ways from the original tumors.

To blast through this bottleneck, a study team led by Dr. Dalvin, in collaboration with Martin Fernandez-Zapico, M.D., a cancer biologist with Mayo Clinic Comprehensive Cancer Center, decided to develop a new, uveal melanoma patient-derived organoid biobank. Their goal is to create a research resource representing the real-world variability of this cancer.

In a paper published in Investigative Ophthalmology & Visual Science, they described the initial development of this biobank. The researchers successfully created organoids derived from Mayo Clinic ocular oncology patients who enrolled in a prospective study involving the collection of tumor tissue for research from July 1, 2019, through July 1, 2024. Their study determined that these organoid models:

• Could be generated, retained their stability through many uses and were a renewable living resource capable of being regenerated at need.
• Retained the clinically relevant features of the original tumors, clustered into appropriate molecular groups based on validated prognostic markers and resembled human disease when compared to in vivo animal models.
• Served as suitable human models for drug screening.

Recognizing the immense value of this organoid biobank, the investigators have already begun expanding it to include other research centers. Their goal is to create a resource capable of representing the global epigenomic variability of uveal melanoma. In the future, they hope this biobank will serve as a comprehensive platform for drug screening and other types of lab research on uveal melanoma. This collaborative effort will accelerate research and pave the way for improved treatments and outcomes for patients with this disease.

Read the paper to learn more about the study, including funding and disclosures.

Mayo Clinic organoid research across the spectrum of disease

Organoids are transforming the landscape of biomedical research. Scientists are using this innovative approach to model diseases, track their progression and identify and characterize potential treatments. Mayo Clinic is at the forefront of organoid research, applying this approach to study a wide range of health conditions including:

• Neurodegenerative and neurological disorders, such as Lewy body dementia, Alzheimer's disease, autism, opioid addiction and alcohol use disorder.
• Measles and other infectious diseases.
• Many types of cancer including breast cancer.
• Inflammatory bowel disease.

The goals of this research extend far beyond its current applications. Mayo Clinic researchers aim to develop organoids representing organs throughout the human body to track disease, screen drugs and regenerate tissues. This approach holds the promise of accelerating research in precision medicine and the search for cures in other areas of biomedical research.

The post 3D models of uveal melanoma offer hope for improved treatments appeared first on Mayo Clinic News Network.