Watch: the Mayo Clinic Minute

Journalists: Broadcast-quality video (1:09) is in the downloads at the end of this post. Please courtesy: "Mayo Clinic News Network." Read the script.

Unlike many cancers that form solid tumors, leukemia is a cancer of the blood-forming cells in the bone marrow.

Dr. Arana Yi says, "Leukemia affects the production of the blood cells and can circulate through all the body from the beginning." 

Leukemia isn't a single disease. There are several types that can behave differently. According to Dr. Arana Yi, "It is a group of cancers with different subtypes. Some develop very quickly, while others progress slowly." 

Leukemia can affect people of all ages. Symptoms can include persistent fatigue, unusual bruising or bleeding, frequent infections, fever, night sweats, unexplained weight loss and shortness of breath. 

"If those are persistent, it is important to review and be evaluated by a doctor for a possibility of a blood count checkup," Dr. Arana Yi mentions. 

Research is helping doctors identify genetic changes that may be driving a patient's leukemia. That information can help guide treatment. 

Dr. Arana Yi says, "This allows us to use targeted medicines, immune-based therapies, sometimes with less traditional chemotherapy or chemo-free regimen." 

Recognizing possible symptoms and seeking medical evaluation can help doctors diagnose leukemia and determine appropriate treatment. 

"Recognizing symptoms since the beginning, and early evaluation with the doctors is key to diagnose the acute leukemia as soon as possible," Dr. Arana Yi concludes. 

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ROCHESTER, Minn. — A large prospective study published today in Nature Medicine found that a blood test designed to detect multiple cancers identified cancer signals across 17 broad cancer types, such as ovarian, lung, breast and colorectal cancers, and many which do not have recommended screening tests.

Mayo Clinic was among the institutions participating in the prospective, interventional study, which enrolled 35,878 adults age 50 and older. Karthik Giridhar, M.D., a Mayo Clinic medical oncologist, was a study investigator and senior author.

The multicancer early detection (MCED) test analyzes small fragments of DNA that cells release into the bloodstream. Researchers use patterns in these fragments to detect signals associated with cancer. When a cancer signal is detected, the test also predicts the likely location of the cancer to help physicians determine appropriate follow-up testing.

Among 32,007 participants included in the study's performance analysis, 287 had a positive MCED test result. Cancer was diagnosed in 173 of those participants. The test had a positive predictive value of 60.3% and specificity of 99.64%. Among participants with a true-positive result, the test correctly predicted one of the two most likely cancer signal origins in 91.3% of cases.

"One of the challenges in cancer screening is that most cancers do not have an established screening test," says Dr. Giridhar. "This study helps us better understand how a multicancer blood test might complement existing screening approaches by identifying cancer signals that otherwise may not be detected through routine screening."

Researchers found that 72.8% of cancers detected by the MCED test were cancer types without U.S. Preventive Services Task Force grade A or B screening recommendations. Among the 151 participants with at least one newly diagnosed primary cancer detected by the test, 53% had stage 1 or 2 disease and 70.9% had stage 1, 2 or 3 disease.

Giridhar also notes that these tests are not yet a substitute for established cancer screenings. Instead, they may supplement existing screening approaches and help expand understanding of cancer detection.

PATHFINDER 2 was a single-arm study, and its endpoints were descriptive, with no comparator group or formal hypothesis testing. The authors say randomized trials and further follow-up are needed to determine the clinical utility of MCED testing in routine clinical practice. The study also used an earlier version of the test that has since been replaced by a commercially available version.

The study was designed and funded by GRAIL Inc., which also participated in data analysis and interpretation and preparation of the manuscript. Dr. Giridhar reports consulting and advisory relationships with GRAIL and other organizations and travel expenses from GRAIL. A complete list of author disclosures is included in the published 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 Multicancer blood test detects 17 cancer types in large prospective study appeared first on Mayo Clinic News Network.

Helix to generate clinical whole genome sequencing and multi-omics data from one million biospecimens, advancing precision medicine as the standard of care

ROCHESTER, Minn. and SAN MATEO, Calif. — Precure, LLC today announced the selection of Helix as its multi-omic laboratory and AI tools provider supporting plans to generate comprehensive molecular data from approximately one million biospecimens and accelerate the integration of molecular insights into routine clinical care at Mayo Clinic and across health systems more broadly.

Less than a week ago, Mayo Clinic announced the launch of Precure, LLC, with founding partner Thermo Fisher Scientific, to help transform how the life sciences community understands the biological changes that occur as disease develops before symptoms occur. Precure, LLC brings together clinical expertise, de-identified longitudinal health information and population-scale molecular data to accelerate the development of new approaches to care.

Helix will provide both advanced AI tools for delivery of genomics into the clinic and biomarker driven research, and population scale multi-omic capability that encompasses clinical whole genome sequencing (WGS) and research grade proteome sequencing. Linked with longitudinal clinical information and high performance compute infrastructure, the objective is to create new opportunities for prevention, diagnosis and treatment.

“Our goal is to generate genomic information that can help inform patient care while creating a powerful resource for discovery,” said Aaron Mangold, M.D., chief medical officer, Precure, LLC. “We are working to make clinical whole genome sequencing and multi-omics a foundation of care, helping us detect disease sooner and act earlier.”

Building on prior work which utilized Helix’s Exome+ ^® sequencing technology, Precure, LLC extends that collaboration by leveraging Helix's experience providing workflow orchestration, (CLIA/CAP) genomic sequencing, data infrastructure, and AI tools to its health system partners. Precure, LLC and Helix have selected Ultima Genomics’ UG200™ Ultra Sequencing Platform as part of the program’s large-scale multi-omics initiative. Helix will use a fleet of Ultima’s next-generation platforms to generate high-quality genomic data for WGS and read-out for proteomics at scale.

“The genome is becoming an enduring patient resource, providing a precision baseline for a lifetime of care,” said James Lu, M.D., Ph.D., CEO of Helix. “Helix brings together the laboratory and data capabilities to make this possible at scale.”

Mayo Clinic's involvement in Precure, LLC is intended to advance its nonprofit mission. Any financial returns to Mayo Clinic would be reinvested in its mission of patient care, research and education. Visit mayo.edu/research/precure for more information.

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About Precure, LLC
Precure, LLC is a Mayo Clinic-controlled company established to generate and responsibly integrate population-scale molecular data with longitudinal clinical information. Precure, LLC creates the infrastructure and scale needed to enable external collaborations, disease-focused discovery and the development of new diagnostics, therapeutics and other healthcare solutions. It complements Mayo Clinic’s investigator-led research and clinical translation activities.

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 Helix
Helix is an enterprise genomics company connecting clinical care and discovery. Its platform brings together clinical sequencing, integration of genomic information into healthcare, and research tools built on linked genomic and longitudinal clinical data. Through its health system partnerships, the Helix Research Network and GenoSphere, Helix helps healthcare and life sciences organizations apply genomics to patient care and the development of new diagnostics and treatments. Learn more at www.helix.com.

Media contacts:

• Tom Millikin, Mayo Clinic Communications, newsbureau@mayo.edu
• Caty Reid, Helix, helix@highwirepr.com

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

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

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

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

Making an aggressive cancer visible again

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

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

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

Turning the target back on

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

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

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

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

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

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

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

A potential strategy beyond thyroid cancer

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

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

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

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

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

Pioneering initiative will generate data at the frontier of healthcare to help transform early biological signals into new opportunities for prevention, diagnosis and treatment

ROCHESTER, Minn. and WALTHAM, Mass. — Mayo Clinic today announced the launch of Precure, LLC, with founding partner Thermo Fisher Scientific, the world leader in serving science, to help transform how the life sciences community understands the biological changes that occur as people move from health toward disease.

Precure, LLC will create one of the world’s leading biomedical datasets through one of the largest human multi-omics data-generation efforts, integrating proteomic, genomic and longitudinal clinical data to help researchers identify early biological signals of disease and provide a foundation for new discoveries in disease biology, diagnostics and therapeutics.

Many diseases begin developing biologically years before symptoms lead to a clinical diagnosis. By connecting molecular and clinical data over time, Precure, LLC has the potential to help researchers better understand these early changes, accelerate drug development and create new opportunities for earlier diagnosis, intervention and more personalized care across a wide range of diseases, such as cancer, cardiometabolic disease, neurological disorders and immune-mediated disease.

Precure, LLC will bring together molecular data generated from one million biospecimens, linked with longitudinal clinical information collected over several years, integrating genomic and proteomic information with Mayo Clinic’s clinical data and expertise in a highly standardized setting. Advanced AI and large-scale data-analytics will be integral to identifying patterns within these complex datasets and translating them into actionable insights. Mayo Clinic will serve as the majority owner of Precure, LLC. Thermo Fisher joins the partnership as a minority owner.

"At Mayo Clinic, we are committed to transforming patient care through innovation," says Gianrico Farrugia, M.D., president and CEO, Mayo Clinic. "By harnessing the full potential of multi-omics data, Precure, LLC aims to help us better understand disease before symptoms appear, accelerating discoveries that can lead to earlier diagnoses, more targeted treatments and better outcomes for patients."

Together, the organizations contribute complementary expertise designed to generate the molecular and clinical data needed to accelerate discovery and translate new insights into advancements in patient care:

• Mayo Clinic combines world-class clinical and research leadership with advanced AI and data science capabilities, extensive biospecimens and longitudinal de-identified clinical data to accelerate discovery and translate insights into advances for patients.
• Thermo Fisher brings industry-leading proteomics expertise and solutions, including its cutting-edge proteomics platform, Olink™ Explore HT, and Thermo Scientific Orbitrap Mass Spectrometry, kits and reagents to help build Precure, LLC’s multi-omics ecosystem.

“Precure LLC has the potential to create a step change in how we generate and apply multi-omics data to improve human health,” said Marc Casper, Chairman and CEO, Thermo Fisher Scientific. “By combining Thermo Fisher’s leadership in scientific technology with Mayo Clinic’s leadership in clinical care, research and innovation, we can create new opportunities at unprecedented scale to detect disease earlier, accelerate drug development and enable more precise therapies.”

Precure, LLC complements Precure Research, Mayo Clinic’s investigator-led scientific effort to understand the biological changes that occur as people move from health toward disease. Precure Research advances the science of identifying and understanding early disease signals, while Precure, LLC provides the scale, infrastructure and collaborations needed to generate population-scale molecular data and help translate discoveries into new diagnostics, therapeutics and other healthcare solutions. Mayo Clinic provides the pathway to validate discoveries and ultimately brings meaningful advances into patient care.

Mayo Clinic's involvement in Precure, LLC is intended to advance its nonprofit mission. Any financial returns to Mayo Clinic would be reinvested in its mission of patient care, research and education.

Visit mayo.edu/research/precure for more information.

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About Precure, LLC
Precure, LLC is a Mayo Clinic-controlled company established to generate and responsibly integrate population-scale molecular data with longitudinal clinical information. Precure, LLC creates the infrastructure and scale needed to enable external collaborations, disease-focused discovery and the development of new diagnostics, therapeutics and other healthcare solutions. It complements Mayo Clinic’s investigator-led research and clinical translation activities.

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 Thermo Fisher Scientific 
Thermo Fisher Scientific Inc. is the world leader in serving science, with annual revenue over $45 billion. Our Mission is to enable our customers to make the world healthier, cleaner and safer. Whether our customers are accelerating life sciences research, solving complex analytical challenges, increasing productivity in their laboratories, improving patient health through diagnostics or the development and manufacture of life-changing therapies, we are here to support them. Our global team delivers an unrivaled combination of innovative technologies, purchasing convenience and pharmaceutical services through our industry-leading brands, including Thermo Scientific, Applied Biosystems, Invitrogen, Gibco, Fisher Scientific, Unity Lab Services, Patheon and PPD. For more information, please visit www.thermofisher.com. 

Forward-Looking Statements Disclaimer
This press release contains “forward-looking statements” within the meaning of applicable securities laws, including statements relating to Thermo Fisher Scientific, Mayo Clinic, and Precure, LLC and its ambitions and potential impact. These statements involve risks and uncertainties that could cause actual results to differ materially. A discussion of these and other risks related to Thermo Fisher Scientific are contained in its most recent reports on Form 10-K and Form 10-Q under “Risk Factors,” available in the “Investors” section of Thermo Fisher Scientific’s website under “SEC Filings.” These statements speak only as of the date of this press release, and all parties disclaim any obligation to update them, except as required by law.

Media contacts:  

• Tom Millikin, Mayo Clinic Communications, newsbureau@mayo.edu
• Jodie Wertheim, Thermo Fisher Scientific, jodie.wertheim@thermofisher.com

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Mayo Clinic researchers are combining biological, environmental and health data with artificial intelligence to identify changes that may signal disease years before clinical symptoms appear 

By the time doctors diagnose Alzheimer's disease, heart failure or cancer, the biological processes behind the illness may have been unfolding silently for years or even decades. 

Mayo Clinic wants to make those invisible years a new target for medicine. 

The healthcare organization is undertaking a sweeping research effort, called Precure Research, to identify the molecular and physiological changes that occur as people move from health toward disease and determine whether doctors can intervene before patients develop clinical symptoms. 

Precure Research initially focuses on diseases of the brain, heart, kidneys, liver and lungs. It brings together genetic information, biological specimens, medical records, environmental exposures, wearable-device data and artificial intelligence (AI). 

The goal is simple: Identify the early stages of disease sooner to improve outcomes. 

Achieving that goal requires answering hard questions. Among the countless biological changes that occur throughout a person's life, which ones reliably signal that disease is beginning, and which can doctors safely do something about? 

Mayo researchers say recent advances are beginning to make that challenge more solvable. 

In one large genetic study, Mayo scientists identified inherited risks for cancer and cardiovascular disease in nearly 2,000 participants, many of whom had no previous indication that they carried the risks. Other Mayo research has found certain precancerous changes that can be detected years before cancer develops. In Alzheimer's disease, scientists increasingly can measure biological changes that begin decades before memory problems become apparent. 

Taken together, those efforts point toward one of medicine’s biggest and transformational ambitions: shifting healthcare from treating established disease to predicting and preventing it. 

Vijay Shah, M.D., Mayo Clinic's Kinney executive dean of research, sees that shift as an extension of Mayo's longstanding approach to medical research: start with an unmet need of the patient, create the knowledge necessary to address it and bring the resulting discoveries back into clinical care. 

"At Mayo Clinic, our research and practice are intertwined," said Dr. Shah. "Everything we do must serve our primary value of putting the needs of the patient first." 

Heidi Dieter, Mayo Clinic's chief research administrator, said the change could ultimately alter the relationship between patients and the healthcare system itself. "We're not just treating disease anymore. We're partnering with people throughout their entire life journey," she said. 

The invisible years 

Doctors have traditionally encountered disease relatively late in its biological history. A tumor becomes visible on a scan. Kidney function declines. A patient develops symptoms of heart failure. Memory problems become noticeable. 

But disease does not begin at that clinical diagnosis. 

Before symptoms emerge, proteins can shift, metabolism can change, immune responses can evolve and environmental exposures can leave measurable biological traces. 

Precure researchers want to reconstruct that progression. 

The initiative combines information from genes, proteins, metabolites and immune signals with longitudinal medical records, environmental information and wearable devices. The approach allows researchers to examine different layers of biology together and how they change over time. 

A person might carry a genetic variant associated with higher disease risk for a lifetime without developing the condition. Researchers hope to understand what happens between inherited susceptibility and actual illness and identify when that trajectory might change. 

But finding a biological signal associated with disease isn't the same as developing a useful screening test. Researchers look for biological signals to develop screening tests that can help physicians intervene early, often when a condition is more easily and effectively treated.  

Looking beyond DNA 

Mayo's approach also extends beyond what is happening physiologically inside the body. 

Researchers are looking beyond genetics and incorporating the exposome, the accumulation of environmental and lifestyle exposures over a person's lifetime and the biological effects they produce. 

Those influences can range from diet, exercise and sleep to pollutants, chemicals and air quality. Researchers increasingly can detect biological traces of some exposures in blood and other specimens and connect them with genetics, clinical histories and geographic information. 

Pilot studies are examining questions including whether long-term air-pollution exposure affects solid-organ transplant outcomes and whether environmental chemicals influence how the body processes medications. Another is testing saliva-based biosensors for biological changes associated with triggers of head and neck cancers. 

Building a biological time machine 

Pulling those pieces together requires infrastructure on a scale that would have been impractical not long ago. 

Mayo says Precure Research ultimately aims to create its largest integrated collection of biological specimens and scientific and health information through Mayo Clinic Platform, connecting what is found in a blood or tissue specimen with molecular measurements, environmental exposures and years of clinical history. 

In effect, researchers want to reconstruct how a patient's biology arrived at a particular disease. 

Precure Research connects molecular information with deep, longitudinal clinical context and Mayo Clinic expertise through existing pathways and infrastructure, such as Digital Pathology, Mayo Clinic Platform and Research Data Atlas, to support research across diseases and data types. The resulting resources are intended to support discovery and translation, including research into biomarkers, diagnostics, therapeutics, clinical trial strategies and new clinical tools. 

AI is central to the strategy because the number of possible relationships quickly exceeds what researchers can examine manually. AI systems can search across genetic variants, proteins, medical records, imaging, environmental measurements and wearable-device readings for patterns that conventional analysis might miss. 

Mayo Clinic is building a research foundation designed to support discovery across diseases, not one study at a time. Connecting clinical information, biospecimens and molecular data at scale can reveal biological relationships that would otherwise remain hidden, allowing an insight from one disease to inform the understanding, prediction or treatment of another. 

A historic institution looks to medicine’s future 

Mayo Clinic is positioned to pursue an ambition as large as Precure Research in part because transforming how medicine is practiced is embedded in its history. 

For more than 160 years, Mayo Clinic has sought fundamentally better ways to care for patients. Its development of the group practice of medicine brought physicians with different specialties together around the needs of an individual patient. Its adoption of a longitudinal medical record gave those physicians something medicine once lacked: data to allow the ability to understand a patient's health not simply at a moment in time, but across years. 

Those innovations changed more than the tools available to physicians. They helped change how medical care was delivered. 

Precure Research is Mayo's next step to extend that history and culture of transformation into a new era. 

The difference is the resolution.

Where a longitudinal clinical record allowed physicians to see a patient's medical history across years, Precure researchers hope to observe the biological history occurring beneath it. 

That ambition also rests on another part of Mayo’s history: patients participating in research. 

Patients who contribute clinical information and biological specimens help researchers identify patterns that no individual patient or physician could reveal alone. Their contributions can help researchers generate knowledge that could lead to better ways to predict, prevent and treat disease, with the potential to benefit patients at Mayo Clinic and beyond. 

By contributing information and specimens over time, patients can help researchers better understand the progression from health to disease and explore opportunities to preserve health for themselves, their families and for future generations. 

From predicting disease to preventing it 

The long-term ambition extends beyond early diagnosis. 

Precure Research will allow for the study of biological processes including inflammation, aging and metabolic dysfunction that cut across diseases traditionally treated by different medical specialties. 

A patient eventually diagnosed with heart failure, kidney disease or dementia might share some underlying biological pathways years earlier. Identifying those mechanisms could give doctors opportunities to intervene before irreversible damage occurs. 

Mayo describes the ultimate objective as extending healthspan, which is the portion of a person's life spent in good health and without significant chronic disease or disability. 

That means identifying not just who is likely to develop a disease, but also when risk becomes actionable and which intervention can alter the trajectory. 

Precure Research is built on the premise that the next major advance in medicine may not come from a single new drug, device or technology, but from understanding human health in ways that avoid disease all together.

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

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

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

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

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

Reading the geography of cancer 

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

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

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

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

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

Linking tumor patterns and immune response 

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

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

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

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

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

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

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

Media contact: 

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

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ROCHESTER, Minn. — Mayo Clinic researchers have identified a potential new approach to treating glioblastoma that could help the immune system fight the aggressive brain cancer while improving the effectiveness of existing chemotherapy.

The preclinical research, published in Nature Communications, found that inhibiting the enzymatic activity of a protein called MALT1 can reprogram immune cells surrounding glioblastomas, shifting them from a state that helps protect the cancer to one that promotes an antitumor immune response.

Researchers also found that treatment with a MALT1 inhibitor slowed tumor growth in preclinical models and that combining MALT1 with temozolomide, the chemotherapy most commonly used to treat glioblastoma, enhanced temozolomide effectiveness. In one preclinical model, median survival substantially increased when this chemotherapy was combined with MALT1 inhibition in comparison to treatment with temozolomide alone.

"Glioblastoma is extraordinarily difficult to treat, in part because the tumor is able to manipulate the immune cells around it and create an environment that protects the cancer. Our findings point to a potential approach to disrupting that protection and, importantly, to making an existing treatment more effective," says Juliana (Hofstatter Azambuja) Yerneni, Ph.D., lead author and researcher in the Department of Laboratory Medicine and Pathology at Mayo Clinic.

Glioblastoma is the most common and aggressive primary cancerous brain tumor in adults and accounts for roughly 5% of malignant brain tumors in children. Despite surgery, radiation and chemotherapy, the cancer remains incurable and almost always returns.

The findings raise the possibility of a future approach that could help patients get more benefit from existing treatments.

"Our goals are to discover how glioblastoma communicates with the immune cells surrounding the tumor in order to dampen the antitumor immune response and to use these discoveries to identify new treatments that enhance antitumor immune response and improve outcomes for patients with this devastating disease," says Linda McAllister-Lucas, M.D., Ph.D., pediatric oncologist, enterprise deputy director for pediatric cancer programs of the Mayo Clinic Comprehensive Cancer Center and co-senior author of the study with Peter Lucas, M.D., Ph.D., vice chair for research in the Department of Laboratory Medicine and Pathology at Mayo Clinic.

More research is needed to determine which specific subtypes of glioblastoma may be most likely to respond to MALT1-targeted therapy and to evaluate its potential for use in patients.

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:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

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ROCHESTER, Minn. — A liver disease affecting nearly 30% of adults worldwide is not a single illness but five biologically distinct subtypes, Mayo Clinic researchers have found. Each carries different risks for heart disease, liver failure, cancer and the need for liver transplantation.

The study, published in Nature Communications and conducted in collaboration with scientists at Virginia Tech, shows that metabolic dysfunction-associated steatotic liver disease has multiple pathways — some tied to obesity and diabetes, others driven by inherited genetic factors.

Notably, genetic subtypes are associated with a higher risk of progression to advanced liver disease, including in patients without typical metabolic risk factors.

The findings could help identify high-risk patients earlier and guide more precise screening and personalized treatment.

"When clinical and genomic data are analyzed together at this scale, you begin to see patterns of disease progression that would otherwise remain hidden," says Shulan Tian, Ph.D., co-senior author and a bioinformatician at Mayo Clinic. "Once you separate these subtypes, you can start to match treatments to the biology that's actually driving the disease."

Metabolic dysfunction-associated steatotic liver disease, formerly called nonalcoholic fatty liver disease, occurs when fat builds up in the liver. It often develops without symptoms but can progress to inflammation, scarring and irreversible damage. It is a leading cause of cirrhosis, liver cancer and transplantation worldwide.

Decoding liver disease at scale

To uncover these subtypes, researchers integrated genetic sequencing with detailed clinical data from more than 4,600 patients with the disease. The dataset spanned a wide range of measures — from liver enzymes, body mass index and lipid levels to coexisting conditions such as diabetes, depression and sleep apnea.

Using advanced computational modeling, the team identified groups of patients who shared underlying biological signals, defining distinct subtypes of the disease.

"What's emerging here is a way to systematically identify meaningful subgroups within complex disease," says Eric Klee, Ph.D., co-senior author and the Everett J. and Jane M. Hauck Midwest Associate Director of Research and Innovation. "It helps us map complex disease with such precision that we can begin to anticipate its course and intervene before the most serious damage occurs."

The discovery was powered by Mayo Clinic's Research Data Atlas, a platform that connects genetic data with patient records to reveal patterns across large populations — a system Dr. Klee helped build. A key component of the Atlas is the Tapestry Study, which has generated Mayo Clinic's largest collection of exome data from more than 100,000 participants. The dataset captures key genetic information that shapes how diseases develop and progress.

"This is exactly the kind of insight large-scale genomic research was built to deliver," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director for the Center for Individualized Medicine who led the Tapestry Study and is a co-author of the research. "When you connect genetic data with detailed clinical information across large populations, you can start to redefine diseases in ways that directly impact patient care."

Liver disease's hidden effects across the body

The study also revealed links beyond the liver. For the first time, researchers found that specific subtypes are associated with conditions such as depression, sleep apnea and migraine, underscoring the disease's broad systemic impact across multiple organ systems.

Next, the team plans to test the approach in broader patient populations and explore how these subtypes respond to different treatments, including therapies such as GLP-1 receptor agonists.

First author Tahmina Sultana Priya, now a Ph.D. student at Virginia Tech, contributed to the research while at Mayo Clinic. For a complete list of authors, disclosures and funding, review the study.

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

Media contact:  

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

The post 5 subtypes of common liver disease discovered — including rapidly progressing genetic forms appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have discovered that chemical signals produced by gut bacteria work together to control intestinal movement. One bacterial signal helps set the intestines in motion, while another primes gut cells to respond more strongly, amplifying the effect.

The research expands scientists' understanding of how the gut microbiome communicates with the body, moving beyond the traditional focus on individual bacteria or bacterial molecules.

The findings, published in the Proceedings of the National Academy of Sciences, point to a potential new direction for microbiome-based treatments: restoring combinations of microbial signals rather than targeting a single microbe or molecule. The strategy could have implications for constipation-predominant irritable bowel syndrome, a chronic condition marked by abdominal pain and constipation.

"The gut microbiome is made up of trillions of microbes producing a vast array of chemical messages that interact with cells throughout the digestive tract," says Purna Kashyap, M.B.B.S., a Mayo Clinic gastroenterologist, director of the Mayo Clinic Microbiomics Program and a senior author of the study. "Deciphering how those signals work in combination gives us a much more precise picture of what is disrupted in disease and what would need to be restored to recover normal function."

How bacterial signals work in combination

Researchers focused on two bacterial molecules: hypoxanthine and butyrate. Earlier Mayo Clinic research found lower levels of both in patients with constipation-predominant irritable bowel syndrome. That finding led researchers to a deeper question: How do these molecules affect intestinal movement?

In the new study, the researchers found that hypoxanthine prompts specialized cells lining the intestine to release serotonin, a chemical messenger that helps move food through the digestive tract. Butyrate works differently. It primes the cells to respond more strongly to hypoxanthine, amplifying the effect.

These specialized cells, called enterochromaffin cells, serve as hubs where different microbial signals come together. They help the gut receive and respond to multiple chemical messages at once.

Researchers followed that chain of events from what happens inside a single gut cell to how contents move through the intestines. They used laboratory-grown intestinal cells, miniature gut models called organoids, intestinal tissue and genetically altered bacteria to piece together each part of the process.

Gianrico Farrugia, M.D., president and CEO of Mayo Clinic and a co-author of the study, is a gastroenterologist whose research has focused on the mechanisms that control gastrointestinal function.

"We have an opportunity to move beyond managing the consequences of disease and toward restoring function for patients," Dr. Farrugia says. "That starts with answering the unanswered questions we see in our patients and following the biology until we understand the mechanism. With that depth of understanding, we can uncover new possibilities for treatment and ultimately advance new cures."

What's next 

Researchers next want to determine whether identifying combinations of microbial signals that are altered in individual patients could eventually help guide treatment. Future research will explore whether restoring complementary signals can improve intestinal movement, with the longer-term goal of developing more precisely targeted microbiome-based therapies.

The research was supported by the National Institutes of Health, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Microbiome Program and other organizations. One or more of the investigators is an inventor of technology related to this research. For a complete list of authors, disclosures and funding, review the study.

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

Media contact:   

• Sharon Theimer, Mayo Clinic Communications, newsbureau@mayo.edu

The post Scientists uncover microbiome signaling system that could open new paths for IBS-related constipation appeared first on Mayo Clinic News Network.