The Regents of the University of California
$100,000 Tower Career Development Grant
Research Title:
Targeting Cell Cycle Dependencies of GNAS Mutant Tumors as a Novel Therapeutic Approach in Mucinous Neoplasia of the Pancreas
Pancreatic cancer is a lethal disease with a 5-year survival of 13%. A subset of pancreatic cancer (15%), arise from precursor lesions known as intraductal papillary mucinous neoplasm (IPMN). The genetics of tumors arising from IPMN is distinct, as these tumors have frequent mutations in the gene GNAS. We recently found that repurposing a drug currently FDA approved for breast cancer, palbociclib, was efficacious in a pancreatic cancer that arose from an IPMN in a single human patient in-vivo, as well as multiple tumor models in vitro. While clinical benefit was observed, the biological mechanism was not determined. Our research plan dissects how the distinct genetics of pancreatic tumors with GNAS mutations confers sensitivity to palbociclib. These data have rapid clinical relevance, as these drugs are already FDA approved, and will be important to identify biomarkers to be used to select patient populations that may receive clinical benefit.