Washington University SPORE in Pancreatic Cancer

PROJECT SUMMARY The Washington University Specialized Program of Research Excellence (SPORE) in Pancreatic Cancer is a highly translational cancer research program focused entirely on the deadliest form of the disease, pancreatic ductal adenocarcinoma (PDAC). Our outstanding investigators have complementary expertise in basic and

clinical studies, and our teams leverage individual expertise in immunology, cancer biology, drug development, genomics, and clinical care to develop novel diagnostic and therapeutic approaches for PDAC. This SPORE application includes three research projects, an administrative core (Core A), two shared-

resource cores [Biospecimen Core (Core B) and Biostatistics and Bioinformatics Core (Core C)], and developmental research (DRP) and career enhancement (CEP) programs. In collaboration with our External (EAB) and Internal (IAB) Advisory Boards, we intentionally selected projects with the greatest potential to impact

the outcome for patients with PDAC. Basic research at WUSM and UPenn has led to the development of the following three research projects, all of which feature innovative investigator-initiated therapeutic trials for PDAC. All projects deemed to have the most potential for translational impact and share an immunologic theme in their

approach. This immunologic theme leverages institutional strengths and highlights our team’s expertise and leadership in this field. Thus far, the immunologic and metabolic therapies that have been increasingly successful for controlling other cancer types have not been impactful in PDAC. Our project leaders have made noteworthy

contributions to elucidate the mechanisms underlying this immunologic resistance and drug resistance in PDAC and developed several exciting strategies with potential to overcome these obstacles. The three projects in this application are designed to have significant potential to change clinical practice within 5-years.

Project 1. Employing CD11b-agonists to render PDAC responsive to immunotherapy Project 2. Mechanisms of Resistance to Neoantigen Vaccines in PDAC Project 3. Targeting Stress-induced MK2 as Novel Strategy in Pancreatic Cancer Our long-term goals are to improve the survival and the quality of life of patients diagnosed with PDAC. To

achieve this goal, we will promote institutional and inter-institutional collaborative research, with an emphasis on translation. We anticipate that no singular approach will solve PDAC and fully commit to supporting the development of novel research concepts as well as highly promising young investigators. Our SPORE will

provide access to pancreatic cancer–specific resources to facilitate this mission.