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October 3, 2018

Mayo Clinic Awarded Nation’s First Hepatobiliary SPORE Grant

By Nicole Brudos Ferrara

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.

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