2021 & 2022 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 funded by Cheryl and Steve Kole, and Rudy Revak
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)
University of Nebraska Medical Center
Award Extension: 2022 Pancreatic Cancer Action Network Precision Medicine Targeted Grant Extension
Award Period: Sept. 1, 2022 – Oct. 31, 2023
Amount: $500,000 ($2,750,000 total since 2017)
He recently joined University of Nebraska Medical Center (UNMC) and the Buffett Cancer Center as the founding director of the Pancreatic Cancer Center of Excellence at UNMC and Nebraska Medicine and the inaugural recipient of the Nancy Armitage Pancreas Cancer Presidential Chair.
Previously, Dr. Hingorani held the Raisbeck Endowed Chair for Pancreatic Research at Fred Hutchinson Cancer Research Center. 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 postdoctoral research at MIT.
Dr. Hingorani has previously been awarded two research grants from PanCAN 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.
Project Overview: 2022 Extension
The Hingorani Lab has developed a pancreatic cancer Mouse Clinical Trials Program (MCTP) to rigorously vet novel treatment strategies through randomized, blinded, placebo-controlled trials in highly faithful genetically engineered models of the disease. The MCTP will help guide the development of new therapeutic arms in the PanCAN Precision PromiseSM clinical trials platform and deepen the knowledge gleaned from patients in these trials. Co-clinical trial testing – evaluating the same investigational drugs in the mouse hospital that are part of the ongoing Precision Promise adaptive clinical trial – allows for bidirectional flow of information to enhance insights into new agents.
The MCTP also allows for combinations identified by the Translational Research Committee (TRC) of Precision Promise to be evaluated within the MCTP. The TRC identifies highly promising therapeutic targets for pancreatic cancer within five key areas of research designated by the acronym PRIME: cancer cell-specific Pathways, DNA Repair mechanisms, Immunomodulators, Metabolism and the tumor Extracellular microenvironment.
In addition, the PanCAN Therapeutic Accelerator Award grant mechanism, which is guided by TRC activities, also provides a peer-reviewed avenue for identifying promising compounds and combinations to be considered for testing in the MCTP. Finally, Dr. Hingorani has the option of testing compounds or combinations that become available and are of high interest without involvement from the Precision Promise team when there are no other Precision Promise-related agents available for testing.