Advancing the Science

Mayo Clinic Medical Science Blog – an eclectic collection of research- and research education-related stories: feature stories, mini news bites, learning opportunities, profiles and more from Mayo Clinic.

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Mon, Nov 5 6:00am · Early-phase Cancer Clinical Trials (Phase I) Available at Mayo Clinic

The Early Cancer Therapeutics Group at Mayo Clinic offers patients whose cancers haven’t responded to standard chemotherapy or other treatments the opportunity to join an early-phase clinical trial of a potential new treatment.

Early-phase clinical trials (phase I) determine safe dosage levels and safe methods of treatment delivery. A phase I clinical trial might be the first time a cancer drug or treatment is used in people. These clinical trials offer investigational cancer solutions for cancer therapy resistance — trials for patients whose cancers haven’t responded to standard treatments.

The Early Cancer Therapeutics Group provides access to the most current phase I trials available from Mayo Clinic researchers, pharmaceutical companies and the National Cancer Institute. Phase I clinical trials are available at all three Mayo Clinic campuses in Arizona, Florida and Minnesota.

The Early Cancer Therapeutics Group website provides information for patients interested in participating in Mayo Clinic’s early-phase clinical trials (phase I).

Mayo Clinic has a new website through which patients and referring providers can learn about its early-phase clinical trials for cancer. The website provides an overview of services offered by the Early Cancer Therapeutics Group, including details on who can be seen, what patients can expect from a visit to Mayo Clinic, and a list of current Early Cancer Therapeutics clinical trials.

For more information on trials available through the Early Cancer Therapeutics Group, or to refer a patient, please contact the Mayo Clinic Cancer Center Clinical Trials Referral Office at 855-776-0015 (toll-free).

Learn more about cancer clinical trials at Mayo Clinic.

Thu, Nov 1 8:54am · Meet the investigator: Roxana S. Dronca, M.D.

At the Mayo Clinic Cancer Center, hundreds of researchers dedicate their professional lives to reducing the burden of cancer. Each one has a unique story. In this video, Roxana S. Dronca, M.D., a hematologist and an oncologist at Mayo Clinic in Jacksonville, Florida, discusses her research on tumor immunology, malignant melanoma and genitourinary malignancies.

Tue, Oct 30 6:00am · Have You Read the September 2018 Issue of Forefront Magazine?

Read about Mayo Clinic’s cutting-edge cancer research in Forefront magazine.

No? This is your chance!

Forefront is the complimentary magazine of the Mayo Clinic Cancer Center. Published in online and email newsletter editions quarterly, Forefront highlights Mayo Clinic’s cutting-edge cancer research.

The September 2018 edition of email/online Forefront features:

View the latest online edition.

View the latest email newsletter.

Subscribe.

Wed, Oct 3 12:00pm · Mayo Clinic Awarded Nation's First Hepatobiliary SPORE Grant

The National Cancer Institute (NCI) has awarded Mayo Clinic an $11.5 million grant to fund  a Specialized Program of Research Excellence (SPORE) in hepatobiliary cancer through August 2023.

Mark A. McNiven, Ph.D.

Headed by principal investigators Mark A. McNiven, Ph.D., and Lewis R. Roberts, M.B., Ch.B., Ph.D., the goal of the Mayo Clinic Hepatobiliary SPORE is to make discoveries and translate them into the clinic for the benefit of individuals diagnosed with or at risk of liver cancer and bile duct cancer.

SPORE grants are designed to promote interdisciplinary research and help basic research findings move quickly from the laboratory to patient care. To earn these competitive grants, institutions must demonstrate a high degree of collaboration between top scientists and clinicians and show excellence in translational research projects. The Mayo Clinic Hepatobiliary SPORE brings together researchers with expertise in basic, translational and clinical science from all three Mayo Clinic campuses in Arizona, Florida and Minnesota.

Lewis R. Roberts, M.B., Ch.B., Ph.D.

This is the first time the NCI has funded a SPORE focused on hepatobiliary cancer, which can be particularly deadly. Less than 18 percent of patients diagnosed with liver or bile duct cancer survive five years or more. The NCI estimates there will be 42,220 new cases of these cancers in 2018, representing 2.4 percent of all new cancer cases, but an estimated 30,200 patients diagnosed with these cancers will die in 2018, representing 5 percent of all cancer deaths. A CDC report released in July 2018 indicated that death rates from liver cancer increased by 43 percent for men and 40 percent for women between 2000 and 2016.

The Hepatobiliary SPORE is comprised of four research projects and three scientific cores designed to consolidate and facilitate the expertise required for effective liver and bile duct cancer research.

The four research projects in the Hepatobiliary SPORE are:

  • Project 1: Fibrolamellar Hepatocellular Carcinoma. This project will study critical genes in human hepatic cells to develop the first diagnostic tests and therapeutic treatments for fibrolamellar hepatocellular carcinoma, a rare form of liver cancer in adolescents and young adults. Project Co-leaders:  Sandy Simon, Ph.D. (The Rockefeller University, New York, NY); Mike Torbenson, M.D.
  • Project 2: Therapeutic Inhibition of Fibroblast Growth Factor and YAP Signaling in Cholangiocarcinoma. This project will examine the cellular mechanisms through which cholangiocarcinoma, or bile duct cancer, develops and progresses. The project team proposes that cross-talk between intracellular signaling pathways within individual cancer cells transmits potent cellular signals, resulting in cancer progression. The team will determine if disruption of these signals results in tumor cell death and therapeutic cancer regression. Project Co-leaders: Gregory J. Gores, M.D.; and Mitesh Borad, M.D.
  • Project 3: Inhibition of SCD1 as a Therapeutic Strategy for Hepatocellular Carcinoma. This project will introduce new concepts that reflect the role of autophagy as a survival mechanism that contributes to therapeutic resistance in hepatocellular carcinoma. It will also focus on targeting stearoyl CoA desaturase 1 (SCD1) metabolic perturbations to reduce therapeutic resistance. Project Co-leaders: John A. Copland, III, Ph.D.; and Tushar C. Patel, M.B., Ch.B.
  • Project 4: Combination Vesicular Stomatitis Virus Viroimmunotherapy and Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma. This project will explore novel immunotherapies for hepatocellular carcinoma, assessing the use of an oncolytic virus expressing an immune stimulatory gene in combination with checkpoint inhibitor antibodies. The project team will also engineer a next-generation oncolytic viral platform tailored to the treatment of hepatocellular carcinoma. Project Co-leaders:  Richard G. Vile, Ph.D.; and Mitesh J. Borad, M.D.

The Mayo Clinic Hepatobiliary SPORE will also develop hepatobiliary cancer investigators through two programs:

  • A Career Enhancement Program led by Dr. Roberts will identify, develop and monitor the progress of the most promising investigators for translational research in hepatobiliary cancer.
  • A Developmental Research Program, led by Edward B. Leof, Ph.D., will attract, develop, support, and monitor the most promising and innovative projects that have the greatest potential to be translated into clinically important applications to reduce the morbidity and mortality of hepatobiliary cancer.

“These projects and programs are designed to identify and develop new scientists in liver and bile duct cancer,” says Dr. McNiven. “I’m hoping this SPORE will help encourage people all around the country and the world to continue to come to Mayo for their liver cancer care.”

Three scientific cores will support SPORE research projects and career development programs:

  • An Administrative Core, led by Dr. McNiven and Dr. Roberts, will provide time and fiscal management and maintain continuous communication within the program and with the NCI and other SPOREs.
  • A Biostatistics Core, led by Chen Wang, Ph.D. and Sumithra J. Mandrekar, Ph.D., will provide statistical, bioinformatics, and computational biology collaboration and data management support.
  • A Biospecimen and Pathology Core, led by Dr. Roberts, Dr. Torbenson, and Mark J. Truty, M.D., M.S., will provide accessioning and processing for new biospecimens with annotated clinical data, with a goal of building a world-class biorepository for hepatobiliary cancer specimens.

The Hepatobiliary SPORE is part of the Mayo Clinic Cancer Center’s Gastrointestinal Cancer Program, which aims to develop and pursue innovative science that will lead to practice-changing outcomes that reduce the incidence of gastrointestinal cancers and increase survival.

The Mayo Clinic Cancer Center has five other current NCI SPORE grants in breast cancer, lymphoma (shared with the University of Iowa), multiple myeloma, ovarian cancer and pancreatic cancer. Mayo Clinic also has a brain cancer SPORE operating under a no-cost extension.

Wed, Jul 11 10:00am · Mayo Clinic-led Study Finds Breast Cancer Survivors Aren't Getting Recommended Number of Mammograms Post-Surgery

Kathryn Ruddy, M.D., M.P.H.

Breast cancer survivors are not getting the recommended level of post-surgery screening, according to a study published in the May 2018 issue of the Journal of the National Comprehensive Cancer Network (JNCCN).  Contrary to screening recommendations, mammography rates decline over time as women get further out from their breast cancer diagnosis; African-American women in particular were less likely to receive the recommended amount of screening.

The study was led by Kathryn Ruddy, M.D., M.P.H., a Mayo Clinic medical oncologist in Rochester, Minnesota and co-chair of the Mayo Clinic Cancer Center Survivorship Cross-disciplinary Group. Dr. Ruddy is also a member of the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology Panel for Survivorship.

“The use of regular mammograms to detect a return of breast cancer before any symptoms appear is associated with better overall survival,” said Dr. Ruddy. “Therefore, clinicians need to make sure that their patients are fully aware of the role these annual mammograms play in screening for new breast cancers as well as for local recurrences. Creating and implementing survivorship care plans with clear follow-up instructions may help ensure that more survivors adhere to recommended screening schedules.”

The researchers followed 27,212 patients for a median of 2.9 years after breast cancer surgery (excluding those who had bilateral mastectomy, for whom mammograms are not needed), with 4,790 patients remaining in the study cohort for at least 65 months.

The retrospective analysis used the OptumLabs Data Warehouse, containing claims from privately insured patients and Medicare Advantage enrollees from across the United States. One year out from surgery, they found 13 percent of the survivors had not undergone any breast imaging. The number without a mammogram within the past year rose to 19 percent by five years after surgery.

Only 50 percent of the patients who were followed for at least five years had at least one mammogram each of those five years.

The study also found that African-American breast cancer survivors were less likely than their white counterparts to receive mammograms according to the recommended schedule. This may contribute to higher mortality rates for that population, given that recurrence of cancer in the breast is considered to be a major driver for poor prognosis in African-American women. While the reasons for this disparity aren’t clear, limited access to genetic testing could be a factor.

There are new tools currently in development to help support and encourage adherence to post-treatment screening guidelines, including mobile apps and web-based programs. Further research is needed to explore how variability in reimbursements for imaging tests may impact surveillance testing.

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This story is based on a May 24, 2018 news release provided by the National Comprehensive Cancer Network.

Mon, Jun 25 6:00am · Targeted DNA next-generation sequencing aids the molecular assessment of pancreatic neuroendocrine tumors

Non-specific image of pancreatic cancer.

Pancreas neuroendocrine tumors (pNETs) are a collection of rare neoplasms distinct from pancreas ductal adenocarcinoma. Although the molecular profile of pNETs is somewhat unclear, advances in molecular tumor genotyping is one area of research that is advancing the understanding of this disease.

In a 2017 article published in OncotargetFerga Gleeson, M.D., M.B., B.Ch., a specialist in gastroenterology and hepatology at Mayo Clinic’s campus in Minnesota, describes a targeted DNA next-generation sequencing (NGS) study conducted at Mayo Clinic.

“Alterations in MEN1 chromatin remodeling genes and mammalian target of rapamycin (mTOR) pathway genes are the most frequent molecular events identified in pNETs,” explains Dr. Gleeson, “But it’s unclear whether these biomarkers and other less frequently observed aberrations possess predictive value.”

The goal of the Mayo study was to assess tumor cytology genotype diversity via endoscopic ultrasound (EUS), and to survey for potential adverse prognostic biomarkers and the prevalence of mTOR pathway variants. “The premise of our research is that molecular tumor genotyping via EUS fine-needle aspiration has the potential to determine a specific tumor’s eligibility for targeted molecular therapy or perhaps immunotherapy, and to facilitate triage of patients into clinical trials based upon their respective tumor genotype,” explains Dr. Gleeson.

Methods

Researchers used a customized 15-gene gastroenteropancreatic neuroendocrine tumor targeted NGS panel evaluating EUS fine-needle aspiration cytology smears from primary pancreas pNETs (90) and pNET liver metastasis (32).

Results

The study yielded a number of interesting results that point to the utility of cytology-based tumor genotyping.

  • 21 percent of primary and 28 percent of metastatic liver pNETs harbored two or more variants per tumor.
  • The most prevalent primary tumor variants were in the MEN1 (42 percent), DAXX (11 percent), ATRX (10 percent) and TSC2 genes (8 percent).
  • Patients harboring aberrations in TSC2, KRAS or TP53 genes were more likely to experience disease progression and reduced overall survival, when compared with individuals who were wild-type.
  • Potential prognostic biomarkers in early disease were observed in 3.3 percent of the primary tumor cohort.
  • The mTOR pathway variants, including alterations in PTEN, TSC2 and PIK3CA, were identified in 10 percent of primary tumors and 12.5 percent of pNET liver metastases.

Conclusions

Ferga Gleeson, M.D., M.B., B. Ch.

This study provides evidence that cytology-based tumor genotyping can reveal a broad spectrum of genetic variants, including possible adverse prognostic biomarkers, reflective of an aggressive phenotype. It also demonstrated the prevalence of potential predictive biomarkers for mTOR pathway inhibitor sensitivity. “We are hopeful that such molecular profiling and patient stratification will become a vital aspect of future efforts to provide individualized and targeted therapy to enhance outcomes for appropriately selected patients,” explains Dr. Gleeson.

Additional research that Dr. Gleeson and colleagues are involved with demonstrates the utility and partnership of EUS with disease-specific and comprehensive cancer gene next-generation sequencing panels, both commercially developed and Mayo developed. When used together, these tools can enhance the evaluation of pancreas ductal adenocarcinoma, pancreas neuroendocrine tumors, gastrointestinal stromal tumors, lung cancer and melanoma.

“Our group’s strength is our collaborative partnership with colleagues in Mayo’s Center for Individualized Medicine and Department of Laboratory Medicine and Pathology to advance the field of DNA and RNA sequencing to further our molecular tumor genotyping capabilities. Our vision is that this will become part of standard clinical care in the field of precision medicine, to offer a customized approached to patient care based upon the molecular profile within a specific tumor or metastatic site.”

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This article was originally published in Cancer Physician Update, a quarterly publication for physicians that discusses trends and advances in hematology and oncology at Mayo Clinic.

Related resources:

Mon, Jun 11 6:00am · Bioartificial liver: Potential to avoid transplant

Schematic of the extracorporeal circuit of the Spheroid Reservoir Bioartificial Liver

Mayo Clinic researchers are planning clinical trials of a bioartificial  liver that might eventually provide an alternative to transplantation for patients with liver failure. Known as the Mayo Spheroid Reservoir Bioartificial Liver (SRBAL), the novel device has been shown to reduce the severity of liver disease and improve survival in laboratory testing on pigs. (Bioartificial organs are comprised of both living tissue and synthetic materials).

“SRBAL has demonstrated ammonia clearance at vastly higher levels than the reports from earlier generations of bioartificial livers,” says Scott Nyberg, M.D., Ph.D., a liver transplant surgeon and biomedical engineer at Mayo Clinic in Rochester, Minnesota. “I foresee a day when we can use these devices as a bridge therapy to transplantation or even to support patients long term and avoid liver transplantation.”

SRBAL would be most appropriate for patients who:

  • Have acute liver failure and are awaiting transplant
  • Have had an overdose of medication, such as acetaminophen, but have a high probability of liver regeneration
  • Aren’t candidates for liver transplant due to another health concern such as cancer, or recent alcohol use

Patients who use SRBAL as a bridge to transplant might utilize the device for an average of one to five days, up to a maximum of two weeks.

Similar to hemodialysis in the treatment of kidney failure, Mayo Clinic’s bioartificial liver functions outside of the patient’s body. However, SRBAL is a “hybrid” extracorporeal device in that it contains hepatocytes of porcine or human origin as a biological source of liver function. The device can maintain functionality of primary hepatoctyes in the range of normal liver physiology — even at the high cell density required for human therapy.

“Our ability to successfully perform liver transplant surgery has led to our biggest problem in this field: the shortage of donor organs,” Dr. Nyberg says. “If we can devise new technologies to avoid liver transplant, we’ve achieved a major accomplishment.”

A quarter century of research

Scott Nyberg, M.D., Ph.D., uniquely trained as both a liver transplant surgeon and biomedical engineer, leads efforts to develop cell-based therapies for the treatment of patients with liver failure and metabolic liver disease.

Dr. Nyberg, who leads Mayo Clinic’s Artificial Liver and Liver Transplantation Laboratory, has devoted more than 25 years to developing the bioartificial liver. The idea came from a mentor during his medical training, who suggested that Dr. Nyberg combine his medical and engineering expertise. His recent research has received funding from the Regenerative Medicine Minnesota initiative.

“As a liver transplant surgeon, I see how serious liver failure is for patients of all ages,” he says. “Liver disease is a world problem. At Mayo Clinic, we’re leading the way internationally with the liver-support device. It’s quite an exciting time.”

The artificial liver and liver transplantation lab has extensive experience in isolating and cultivating primary hepatocytes for use in cellular therapies. The lab uses genetically engineered pigs with a homozygote deficiency in fumarylacetoacetate hydrolase (FAH) — the first large animal models of hereditary tyrosinemia type 1 (HT1) in hereditary metabolic liver disease. The phenotype of FAH-deficient also includes spontaneous cirrhosis, portal hypertension and possibly hepatocellular carcinoma. The porcine model could potentially allow for the large-scale production of high-quality human hepatocytes needed in order for bioartificial livers to be incorporated into clinical use.

About 38,000 people in the United States die each year from liver disease, according to the Centers for Disease Control and Prevention. “Acute liver failure claims the lives of over 30 percent of people who are diagnosed with it. Liver transplantation has been the go-to option for treatment, but it comes with many risks and isn’t always an option, due to compatibility and availability of donor livers,” Dr. Nyberg says. “A bioartificial liver device could allow physicians to treat and extend the lives of more patients, safely and cost-effectively, with fewer risks.

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This article was originally published in Cancer Physician Update, a quarterly publication for physicians that discusses trends and advances in hematology and oncology at Mayo Clinic.

Related resources:

Thu, Mar 22 9:00am · Mayo researchers identify characteristics of colon polyps most likely to progress to cancer

Lisa Boardman, M.D.

Researchers at Mayo Clinic are closer to answering the question, why does one colon polyp transform to cancer while another seemingly identical polyp does not? A colon polyp is a small clump of cells that forms on the lining of the colon. While most colon polyps are harmless some can develop into colon cancer, which can be fatal if found too late.

“The molecular determinants that distinguish normal, benign polyps from those at risk for becoming cancer are unclear,” says Lisa Boardman, M.D. a gastroenterologist at Mayo Clinic. “In our paper, published in the journal Scientific Reports, we asked the question: why does one polyp transform to cancer while another, that is clinically and histologically identical, does not?”

To answer this question, Dr. Boardman and her colleagues used next-generation sequencing techniques to molecularly characterize and compare colorectal polyps from Mayo Clinic patients that were associated with cancer with those from patients with polys that were benign.

Next-generation sequencing is sophisticated DNA and RNA sequencing technology which allows researchers to study biological systems at a level never before possible.

Dr. Boardman and her colleagues found that polyps adjacent to cancerous tissue exhibited distinct genetic alterations from polyps that remained cancer free. “By integrating multiple sequencing platforms, we identified a panel of 124 genes that were differentially altered between polyps that were associated with cancer and polyps that did not progress to colorectal cancer,” she says. “These results serve as a foundational study showing that polyps with and without cancer exhibit distinct molecular signatures.”

Dr. Boardman says the ability to identify molecular features that predict whether a polyp will transform to cancer would be a major clinical step in individualizing the care of patients with polyps. She says current national guidelines for polyp surveillance are still based only upon polyp size, number, histology and degree of dysplasia. She adds that there are currently no blood or tissue-based molecular tests used to tailor surveillance intervals for patients with polyps.

Dr. Boardman says the ability to determine a polyp’s risk for progression to cancer could have significant benefits for patients and the health care system including reducing costs, reducing risks and improving the use of colonoscopy. “This study is also the first step in our efforts to establish a pre-cancer biobank at Mayo Clinic, which will support future studies on polyps in order to prolong health by preventing pre-malignancy in the colon.”

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