2021 Grantee: Sunil R. Hingorani, MD, PhD
Fred Hutchinson Cancer Research Center
Research Project: Murine Clinical Trials for the Evaluation of High Priority Therapeutic Targets for Precision Promise
Award: 2021 Pancreatic Cancer Action Network Precision Medicine Targeted Grant Extension
2017 Pancreatic Cancer Action Network Precision Medicine Targeted Grant funded by 1440 Foundation
Award Period: July 1, 2021 – June 30, 2022
Amount: $500,000 ($2,250,000 total since 2017)
Dr. Hingorani is a medical oncologist and cancer biologist specializing in pancreas cancer. He holds the Raisbeck Endowed Chair for Pancreatic Research and is professor with joint appointments in the Clinical Research and Public Health Sciences divisions at Fred Hutchinson Cancer Research Center. He is also Professor of Medicine in the Division of Medical Oncology at University of Washington School of Medicine. He received a BS in Molecular Biophysics and Biochemistry from Yale College and a PhD in Cellular and Molecular Physiology and an MD from Yale University. He completed a fellowship in Hematology and Oncology at Dana-Farber Cancer Institute in Boston and performed postdoctoral research at MIT.
Dr. Hingorani is the founding director of the Pancreas Cancer Specialty Clinic at the Seattle Cancer Care Alliance, a real-time multidisciplinary clinic that serves as the focal point for a comprehensive translational research program in pancreas cancer, the Center for Accelerated Translation in Pancreas Cancer (CATPAC), which he also directs. Dr. Hingorani has previously been awarded two research grants from the Pancreatic Cancer Action Network and is a member of our Scientific & Medical Advisory Board.
Through his early-career PanCAN grant funding, Dr. Hingorani and colleagues developed a mouse model genetically programmed to develop pancreatic cancer that closely mimics human disease progression. Building upon that extraordinary contribution to the field, Dr. Hingorani has established a start-of-the-art comprehensive mouse hospital that allows robust evaluation of therapies in a clinically relevant animal model.
Drug development for pancreatic cancer has historically been too slow, too expensive, and it’s resulted in too few treatment breakthroughs. PanCAN’s Precision PromiseSM adaptive clinical trial is designed to be more efficient, requiring fewer patients and less time and money than a traditional clinical trial, accelerating the rate of progress for new treatment options. Through its adaptive nature, Precision Promise can test multiple investigational treatment options against standards of care in patients with metastatic pancreatic cancer, as well as incorporate best-in-class supportive care measures. However, identifying promising investigational agents and combinations to test within the Precision Promise platform remains a challenge.
Through Dr. Hingorani’s project extension, potential treatment approaches can be rigorously tested in his mouse hospital in a clinical trial setting, comparing investigational agents to FOLFIRINOX combination chemotherapy in mice, to quickly identify the most promising agents to incorporate into a study with patients. This strategy allows head-to-head comparison of investigational treatments, which wouldn’t be possible when evaluated in different lab settings. Through his prior funding for this grant, Dr. Hingorani established rigorous principles for the pre-clinical evaluation of new therapies: pilot studies are first performed on modest-sized cohorts (5-7 animals per arm) treated for 28 days (equivalent to 1 cycle of therapy), and the most promising strategies are then advanced to full survival studies. Dr. Hingorani and his team evaluate multiple endpoints including changes to the tumors and tissue-based measures in the mice to determine efficacy in order to decide which strategies to advance. The last several years of grant funding has demonstrated that the approach has been successful in narrowing down investigational drugs that aim to modulate the patient’s immune system or impact the tumor’s microenvironment.
The additional year of funding will allow the Hingorani lab to accomplish three specific aims – identify treatment regimen(s) that are superior to FOLFIRINOX in the pre-clinical mouse clinical trial model; determine if the mouse platform can be used to predict clinical outcome; and provide a foundation for eventual studies to determine if targeting specific compartments within pancreatic cancer through distinct mechanisms provides a therapeutic advantage.