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

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

Highlights include:

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

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

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

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

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

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

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

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

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

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

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

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

About Mayo Clinic Comprehensive Cancer Center 
Designated as a comprehensive cancer center by the National Cancer Institute, Mayo Clinic Comprehensive Cancer Center is defining the cancer center of the future, focused on delivering the world's most exceptional patient-centered cancer care for everyone. At Mayo Clinic Comprehensive Cancer Center, a culture of innovation and collaboration is driving research breakthroughs in cancer detection, prevention and treatment to change lives.

Media contact on-site at ASCO:

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

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

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

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

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

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

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

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

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

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

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

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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 Mayo Clinic researchers develop first salivary gland regenerative biobank to combat chronic dry mouth appeared first on Mayo Clinic News Network.

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

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

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

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

Seeking a bladder cancer cure

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Editor's note: May is National Cancer Research Month, and May 20 is Clinical Trials Day.

A cancer diagnosis is an emotional experience. Learning that you have cancer can create feelings of hopelessness, fear and sadness. This is especially true if your cancer is advanced or available treatments are unable to stop or slow its growth.

"Often, when patients are diagnosed with cancer, they feel hopeless and scared. Clinical trials are one way patients can be proactive. They can make a choice in how their care is going to be," says Matthew Block, M.D., Ph.D., a Mayo Clinic medical oncologist.

Cancer clinical trials help physician-scientists test new and better ways to control and treat cancer. During a clinical trial, participants receive specific interventions, and researchers determine if those interventions are safe and effective. Interventions studied in clinical trials might be new cancer drugs or new combinations of drugs, new medical procedures, new surgical techniques or devices, new ways to use existing treatments, and lifestyle or behavior changes.

Clinical trials provide access to potential treatments under investigation, giving options to people who otherwise may face limited choices. "Clinical trials open the door to a new hope that maybe we can fight their cancer back and give them a better quality of life," says Geoffrey Johnson, M.D., Ph.D., a Mayo Clinic radiologist, nuclear medicine specialist and co-chair of the Mayo Clinic Comprehensive Cancer Center Experimental and Novel Therapeutics Disease Group.

You will receive cancer treatment if you participate in a clinical trial. "I think one common misperception about clinical trials is that if you enter a clinical trial, you may not get treatment (receive a placebo). And that's actually very much not true. Most clinical trials are looking at one treatment compared to another treatment," says Judy C. Boughey, M.D., a Mayo Clinic surgical oncologist, chair of Breast and Melanoma Surgical Oncology at Mayo Clinic in Rochester, Minnesota, and chair of the Mayo Clinic Comprehensive Cancer Center Breast Cancer Disease Group.

"I think one common misperception about clinical trials is that if you enter a clinical trial, you may not get treatment (receive a placebo). And that's actually very much not true. Most clinical trials are looking at one treatment compared to another treatment."Judy C. Boughey, M.D.

Watch this video to hear the experiences of people who have participated in cancer clinical trials and to hear Drs. Block, Johnson and Boughey discuss the importance of clinical trials in cancer care:

Clinical trials are a significant part of cancer care at Mayo Clinic Comprehensive Cancer Center. Cancer care teams work together across specialties to make sure the right clinical trials are available to serve the needs of people with cancer who come to Mayo Clinic.

"We are very particular in how we select the clinical trials that we have available for patients," says Dr. Boughey. "We want to have the best trials available for our patients. Some of the clinical trials are evaluating drugs — we are so excited about those drugs, but we can't prescribe those drugs for patients without having that trial. And so we will actually fight to try to get that trial open here to have it available as an opportunity for our patients."

If you choose to participate in a clinical trial, you will continue to receive cancer care. "For most patients that we evaluate, there's always the standard of care treatment option for those patients. And then, in many situations, there's also a clinical trial that the patient can participate in," says Dr. Boughey.

People who participate in clinical trials help make new and better cancer care available for future patients. The treatments available for cancer patients today exist because of the clinical trial participants of yesterday. "We couldn't advance medicine if it wasn't for people volunteering for trials. And the promise from our side is to say we're not going to put patients on trials or offer trials for them to consider unless we think there's a good chance that they'll get a benefit or that society at large will get a benefit," says Dr. Johnson.

"We couldn't advance medicine if it wasn't for people volunteering for trials. And the promise from our side is to say we're not going to put patients on trials or offer trials for them to consider unless we think there's a good chance that they'll get a benefit or that society at large will get a benefit."Geoffrey Johnson, M.D., Ph.D.

Participating in a clinical trial may give you access to cutting-edge treatment, improve your quality of life and extend your time with loved ones.

"It's definitely worth reaching out to your healthcare provider and asking, 'What clinical trials could I be a potential candidate for?'" says Dr. Boughey. "And remember, you can ask this of your surgical oncologist, your medical oncologist, your radiation oncologist, or any of the physicians you're seeing because there are trials in all disciplines. There are also ongoing trials that require the collection of tissue or the donation of blood. They can also be important in trying to help future generations as we continue to work to end cancer."

Participating in a clinical trial is an important decision with potential risks and benefits. Explore these FAQ about cancer clinical trials, and ask your care team if a clinical trial might be right for you.

This article first published on the Mayo Clinic Comprehensive Cancer Center blog.

The post Clinical trials: A significant part of cancer care appeared first on Mayo Clinic News Network.

Mayo Clinic operates one of the largest clinical laboratories in the world. More than 87,000 samples pass through the labs from Mayo Clinic patients and Mayo Clinic Laboratories' clients per day. At Mayo Clinic Laboratories and the Department of Laboratory Medicine and Pathology (DLMP), these thousands of samples are tested for a large swath of molecules that can signal disease. Additionally, Mayo Clinic physicians and researchers develop new diagnostic tests every year. The innovation and capability to improve medicine fuels the work of clinical pathologist Akhilesh Pandey, M.D., Ph.D. 

"The fact that we, as researchers, can find a new biomarker associated with a disease, develop a test to find it sooner and implement it into clinical practice, places Mayo Clinic at the forefront of the medicine of the future," he says.  

Dr. Pandey's multidisciplinary research team consists of chemists and biochemists, molecular and computational biologists and experts in advanced biomedical instrumentation who push the boundaries of technology to develop more powerful tests to help detect and diagnose diseases earlier.

"Our lab is focused on problems and technologies where there is a direct and tangible path to discovering new findings that can be put into medicine in many ways, especially in terms of diagnostics. For us, it's all about translating research into the practice," he says.

He collaborates with more than 100 different researchers at Mayo Clinic to achieve this.

"DLMP consultants and staff are continually searching for ways to translate clinically relevant research findings into novel diagnostics that will provide our clinicians and patients the answers they need. Many of these findings come from our own investigators in DLMP or Mayo Clinic, but we also will keep abreast of advances from researchers worldwide. Our track record is impressive due to the efforts and creativity of consultants like Dr. Pandey and so many others," says Eric Hsi, M.D., chair of the Department of Laboratory Medicine and Pathology at Mayo Clinic.

Research and Practice 

One group of genetic disorders that is particularly challenging to diagnose is called sphingolipidosis, which stems from the harmful accumulation of sphingolipids, a type of lipid molecule. Tay-Sachs disease is a form of sphingolipidosis where these lipids build up in the brain and spinal cord, causing nerve cell damage.

Most tests for sphingolipidosis can only screen for one specific form of the disorder at a time, targeting about 10 molecules, which makes the process laborious and time-consuming for both clinicians and patients. 

Dr. Pandey and researcher Seul Kee Byeon, Ph.D., heard about this challenge from colleagues in Mayo Clinic's Department of Laboratory Medicine and Pathology. So they went to work designing a more efficient test.

The result: a single assay that can test for 47 different molecules linked to many kinds of sphingolipidosis, offering more efficient diagnostic testing.  

"It's a huge gain, especially for clinicians who may suspect a patient has a rare and serious genetic condition but may not know where in the pathway the problem lies," says Dr. Byeon, who is the lead author on a study reporting the findings in the journal Clinical Chemistry.

This new test is still in development but will be rolled out for use in the near future at Mayo Clinic Laboratories. Dr. Byeon is also working on the next iteration of this assay, which would target hundreds of lipids. 

From just one cell

Dr. Pandey's research teams in the Systems Biology and Translational Medicine Laboratory and the Advanced Diagnostics Laboratory use a sensitive but versatile technique called mass spectrometry to detect, identify and quantify molecules in lab samples, which can come from blood, tissue or other specimens.

In addition, Dr. Pandey's team conducts research using single-cell proteomics and single-cell lipidomics, which can uncover what proteins and lipids, respectively, are present in individual cells. They also apply a rapidly evolving approach called spatial biology to map where various molecules are in a specific tissue. 

The information gleaned from these analytical techniques can lead to the discovery of biomarkers for a variety of conditions, from genetic disorders to cancer. 

"We want to find the next generation of biomarkers and we have the technology to do it," he says. 

Dr. Pandey's multidisciplinary research team has several other notable projects underway aimed at advancing diagnosis and treatment for a variety of diseases and disorders including: 

• Multiple myeloma: Working to identify which patients with this blood cancer will respond to a certain class of drugs that stimulates the immune system to attack abnormal cells.
• Cholangiocarcinoma: Helping gastroenterologists detect this form of bile duct cancer using single-cell proteomics, which illuminate protein behavior in individual cells, with the goal of detecting this difficult-to-treat cancer earlier.
• Inherited metabolic disorders: Adapting a blood-based test that detects genetic defects in a complex chemical process known as glycosylation so that it can be used to detect metabolic changes associated with cancer. 
  

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

The post Advancing medicine one lab test at a time appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A new study by Mayo Clinic Comprehensive Cancer Center researchers found that the presence of a specific genetic mutation — KRAS circulating tumor DNA (ctDNA) — strongly indicates a higher risk of cancer spread and worse survival rates for patients with pancreatic ductal adenocarcinoma (PDAC). The mutation was identified using a readily available and clinically approved blood and abdominal fluid test.

PDAC is an aggressive form of cancer that is often difficult to diagnose. Most patients already have cancer spread to other parts of their body when initially diagnosed, and current tests often miss this hidden spread. This makes it challenging to determine the best treatment strategy. The findings, published in the Annals of Surgical Oncology, may help identify patients who are more likely to have cancer spread to other parts of the body, therefore providing doctors and patients with the right information to make informed decisions about treatment.

"This is a major advancement for pancreatic ductal adenocarcinoma," says Mark Truty, M.D., hepatobiliary and pancreatic surgical oncologist within Mayo Clinic's Department of Surgery. Dr. Truty is senior author of the study. "We've had this genetic testing available for a number of years, however, we did not know the significance of the results or how to interpret them. Having the KRAS status will allow the patient and their provider to make better decisions about their individual cancer treatment."

The prospective cohort study, involving nearly 800 patients — the largest patient series to date in the literature using ctDNA — found that 20%-30% of patients with PDAC have detectable mutant KRAS ctDNA in the blood and/or peritoneum, and that those without any previous treatment, such as chemotherapy, had the highest incidence. Thus, the study suggests that ctDNA assays should be performed prior to treatment to have the highest yield.

The researchers examined data between 2018 and 2022. Blood sample tests revealed that 104 patients (14%) had KRAS ctDNA mutation. These patients were more likely to develop advanced, spreading cancer and had a lower survival rate. Further testing of fluid from around the abdominal cavity in 419 patients showed similar results: 123 (29%) had the marker, and these patients also experienced worse outcomes. The presence of this marker, whether in blood or abdominal fluid, indicated a poorer prognosis.

The study highlights that while surgery is the only known cure, most patients experience cancer spread after surgery. The test helps identify patients less likely to benefit from surgery alone, guiding treatment decisions towards chemotherapy and/or radiation before surgery. For patients without the KRAS mutation (approximately 10% of cases), the test is less conclusive and other tests are needed.

"Historically, we've known that KRAS mutations are associated with a more biologically aggressive pancreatic cancer," says Jennifer Leiting, M.D., hepatobiliary and pancreatic surgeon within Mayo Clinic's Department of Surgery. Dr. Leiting is first author of the study. "But this large study gives us a much clearer understanding of how to interpret the test results and use them to improve patient care. It allows for more accurate staging at diagnosis, leading to better treatment decisions."

The researchers suggest that this test should become a standard part of the initial diagnosis for PDAC, enabling more personalized risk stratification and effective treatment plans.

"This improved diagnostic capability offers hope for patients and their families facing this challenging disease," says Dr. Truty. "It's optimistic to see how advances in genetic testing are directly helping our patients."

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

About Mayo Clinic Comprehensive Cancer Center 
Designated as a comprehensive cancer center by the National Cancer Institute, Mayo Clinic Comprehensive Cancer Center is defining the cancer center of the future, focused on delivering the world's most exceptional patient-centered cancer care for everyone. At Mayo Clinic Comprehensive Cancer Center, a culture of innovation and collaboration is driving research breakthroughs in cancer detection, prevention and treatment to change lives.

Media contact:

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

The post Mayo Clinic researchers identify a measurable genetic mutation as a significant predictor of metastasis and survival in pancreatic cancer appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A discovery by Mayo Clinic researchers may help explain why immunotherapy hasn't been helpful for many patients with metastatic colorectal cancer. In findings published in Clinical Cancer Research, the team identified specific proteins — fibronectin and smooth muscle actin — within colorectal cancer tissues that are associated with resistance to immunotherapy treatment.

Immunotherapy is a major advance in treating cancer, but many patients, including those with metastatic colorectal cancer, do not respond to it. Until now, researchers have not known why.

"We need predictive biomarkers to guide the selection of immunotherapy for patients," says medical oncologist and gastroenterologist Frank Sinicrope, M.D., the senior author of the study. "Identifying those who may have resistance to treatment can be useful, because then we can spare them from receiving treatment that may not be beneficial and could produce significant toxicities."

The research team used digital spatial profiling, an advanced technology that simultaneously analyzes the expression of multiple proteins and where they are located within tissues. This approach allowed researchers to zoom in to get a bird's eye view of a tumor that includes proteins both within and surrounding the tumor cells and how they interact.

Dr. Sinicrope compares the spatial tools to an aerial view of a neighborhood where one can see relationships between driveways, houses, yards and neighboring structures. Similarly, this detailed view provides physicians and researchers with critical information about the proteins in and around a patient's cancer, potentially informing the best treatment for the patient. 

"We wanted to learn more about the patients who did not respond to immunotherapy. We investigated the leading edge of the tumor where cancer cells are invading and where the immune system is attempting to fight the cancer," says Dr. Sinicrope. "It's like a battle going on here and we're getting a snapshot into who is in attendance."

The researchers focused on 10 regions at the invasive margin of a tumor. They applied digital spatial profiling to investigate 71 distinct proteins in both the tumor's epithelial compartment and the surrounding stromal compartment. Fibronectin and smooth muscle actin are two extracellular matrix proteins that were found in the epithelial region of the tumor and were associated with resistance to immunotherapy and shorter time before disease progression.

Upon further analysis, the researchers observed that cancer-associated fibroblasts were producing these proteins. The evidence, they say, suggests that these proteins can contribute to suppression of the anti-tumor immune response.

The discovery offers a step toward more personalized and effective colorectal cancer treatments.  

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. 

About Mayo Clinic Comprehensive Cancer Center 
Designated as a comprehensive cancer center by the National Cancer Institute, Mayo Clinic Comprehensive Cancer Center is defining the cancer center of the future, focused on delivering the world's most exceptional patient-centered cancer care for everyone. At Mayo Clinic Comprehensive Cancer Center, a culture of innovation and collaboration is driving research breakthroughs in cancer detection, prevention and treatment to change lives.

Media contact:  

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

The post Mayo Clinic researchers identify proteins linked to immunotherapy resistance in metastatic colorectal cancer appeared first on Mayo Clinic News Network.

"Location, location, location" may be a familiar mantra in real estate, but in the world of biology, it's proving just as essential. Spatial biology is a rapidly evolving field that maps the precise location of molecules within cells and tissues. It is changing the way biomedical research is conducted, spurring advances in our understanding of health and disease.

"Spatial biology allows us to study how the local environment influences cellular interactions and behavior," says Tamas Ordog, M.D., professor of physiology at Mayo Clinic and director of the Spatial Multiomics Core. "In all honesty, you can hardly find a problem in biology and medicine that is not a spatial problem."

Unlike traditional methods that analyze biological samples in bulk or as single cells, spatial biology uses sophisticated techniques to study molecules in their natural context. The approach marries old-school histology methods involving stains and microscopy with modern-day tools like sequencing and mass spectrometry.

For example, researchers can attach unique molecular "barcodes" to specific targets, such as RNA or proteins, while preserving their position within the architecture of the tissue. They then use high-resolution fluorescent microscopy to "read out" the barcodes to identify the tagged molecules at their location.

Alternatively, they can incorporate location barcodes into the "libraries" of molecules collected from the histological specimens, allowing the simultaneous detection of the targeted RNA or proteins and their location by sequencing. They then decode the barcodes associated with the molecules and combine that information with the spatial data to create maps showing how the molecules are spread across the tissue.

Dr. Ordog says he and his team often refer to their work as "spatial multi-omics" because it integrates multiple layers of "omics" data (such as genomics, epigenomics, transcriptomics and proteomics) with spatial information.

"Soon, we will be able to generate an insane amount of information within a very short time with the technologies out there," he says.

This information — which charts where specific molecules are located and how they interact in space — gives scientists a much more detailed, dynamic view of biology. It's particularly transformative in studying diseases like cancer, where the tumor microenvironment plays a key role in disease progression and treatment response.

"Cancer is often a mass of tissue, and the cells that sit inside can behave quite differently depending on whether the tumor is infiltrated by immune cells or only surrounded by them," says Dr. Ordog. "Spatial biology can help us interrogate these interactions."

This emerging discipline can also help researchers tease apart the multiple cell types that make up atherosclerotic plaques, a key feature in the development of cardiovascular disease. And, in the case of Dr. Ordog's own research, it can give insight into how cell-to-cell interactions give rise to diabetic complications of the gastrointestinal tract.

"In diabetes, metabolic dysfunction influences various regulatory cells in the muscle layer of the gut," he says. "We can use spatial biology to assess which cells are more prone to metabolic damage than others."

By revealing how cellular environments shape various biological processes, Dr. Ordog says spatial biology can contribute to the understanding of disease and lead to more precise, personalized medical treatments.

"We can apply these sophisticated discovery techniques to routine patient samples, and in this way shorten the time it takes to translate basic research findings into advances in clinical care," he says.

The post Spatial biology puts potential disease targets in their place appeared first on Mayo Clinic News Network.

A recent Mayo Clinic study sought to understand the connection between a mother and son's health conditions and, along the way, discovered a broader implication for patients suffering from immunodeficiencies.

Researchers revealed what appeared to be two separate health conditions — a mother's cancer and her son's persistent viral infections — stemmed from a single, shared genetic variant in what is known as the IRF8 gene, an important component of the immune system.

On the surface, the son's and mother's clinical presentations appeared worlds apart. The son had a persistent Epstein-Barr virus infection along with numerous respiratory issues, whereas the mother had developed human papillomavirus (HPV)-related cancer.

Typically, the son would have been seen by infectious disease and pulmonary specialists while the mother would have gone to a gynecologist, with hardly any chance of professionals seeing a connection between the two and their respective conditions.

However, the boy's case, coupled with the discovery that his mother shared the same IRF8 variant and had developed an HPV-related tumor, sparked a deeper investigation among physicians and researchers at Mayo Clinic. Two Mayo clinicians, Thomas Boyce, M.D., initially, and Elizabeth Ristagno, M.D., subsequently were instrumental in acting as a bridge between the practice and research in this case.

"Finding the variant and proving its effect on the patients' immune systems made it clear that their different clinical manifestations had the same underlying biological cause," says Amir Sadighi Akha, M.D., D.Phil., a consultant and laboratory director at the Department of Laboratory Medicine and Pathology at Mayo Clinic, the co-senior author of the study. "In a way, our findings gave their condition a name."

Researchers emphasized the importance of team science in this achievement and that no single group has the expertise to tackle a study like this alone.

In this respect, the work done by a group led by Dan Billadeau, Ph.D., chair of the Department of Immunology and co-senior author of the paper, was crucial to understanding how this variant carries out its effects, says Dr. Sadighi Akha.

"Working on immunodeficiencies is exciting and challenging at the same time, particularly when the disease under study is extremely rare, such as this one," Dr. Billadeau says. "The only way to do it is through concerted efforts by physicians and scientists in different disciplines, as was the case here."

"The more we did, the more the effect of this genetic variant came into focus, and the more excited we became," Dr. Sadighi Akha says.

They underscore that the more people know about these diseases and their consequences, the more beneficial it could be to both patients and the broader understanding of immunological diseases, including how they lead to increased risk of infections and cancers.

They note that the methods used in this study and its findings could help identify other cases of immunodeficiency and play a role in deciding how best to treat them.

They also believe that Mayo Clinic is among a select group of institutions that can undertake this type of work.

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

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Mayo Clinic researchers have discovered a new role that a specific protein plays in regulating cell resistance and fighting tumors in certain types of cancer, offering hope for improved cancer therapies and patient outcomes.

The protein, known as NKG7, is found in CD8+ T cells, a type of immune cell that can recognize and kill cancer cells. CD8+ T cell resilience is essential for anti-tumor activity. The protein allows CD8+ T cells to continue killing cancer cells even under stress and can help prevent cancer from growing and spreading.

"We found that patients with invasive bladder cancer who had NKG7-expressing CD8+ T cells within their tumor had superior survival compared to patients without," says Dan Billadeau, Ph.D., senior author of the study, detailed in Nature Communications. "This discovery holds promise for manipulating CD8+ T cells — for example, CAR-T and tumor-infiltrating lymphocytes (TILs) — to combat cancer."

T cell-based immunotherapy is a developing field that treats many types of cancers. However, Dr. Billadeau explains that a significant problem in using these therapies is that many patients may experience a transient or short-term response followed by cancer progression.

There are two main types of T-cell-based therapies:

CAR T-cell therapy takes T cells from patients and modifies them to express a chimeric antigen receptor (CAR). CARs are proteins that recognize specific antigens on cancer cells, allowing the T cells to target and kill cancer cells more effectively.  

TIL (tumor-infiltrating lymphocytes) therapy involves taking T cells from a patient's tumor and growing them in a lab. Then, the cells are returned to the patient in a higher dose.

NKG7 is a protein expressed in cytotoxic lymphocytes like CD8+ T cells and natural killer cells. A prior Mayo Clinic study had linked it to durable responses from anti-PD-1 immunotherapy in patients with melanoma, a skin cancer. However, the mechanism remained unclear.

Dr. Billadeau says that in this new work, the team investigated how the NKG7 protein might make CD8+ T cells more resilient and able to combat cancer cells more efficiently.

"We showed that NKG7 works at the lysosome, an organelle in the cell's cytoplasm, to restrain the overactivation of mTOR, a protein that regulates cell growth and which limits the persistence of functional CD8+ T cells," says Dr. Billadeau. "We discovered a role of NKG7 in the longevity of effector CD8+ T cells that are crucial in the control of cancer progression."

The manipulation of NKG7 expression can be used in CAR-T and TIL therapy to enhance their function and increase anti-cancer responses. The findings may also aid in cancer prognosis, as high NKG7 expression in CD8+ T cells in a tumor might correlate with a better clinical outcome. The NKG7 levels in CD8+ T cells in cancer tissues and peripheral blood may predict responses to immune checkpoint inhibitor therapy, another therapy that helps the immune system fight cancer, but this needs further validation.

Next steps

The team's work suggests that providing NKG7 proteins to various CD8+ T cell therapies, such as CAR-T and TIL, will give these T cell therapies a more resilient phenotype, leading to better patient outcomes. The team is working on several projects to add NKG7 to these therapies and test them in animal models. They are also performing studies in other cancers to use CD8+/NKG7+ T cells to predict survival and response to different cancer immunotherapies.

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

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