SUMO Inhibition and Irinotecan: A Novel Synergistic Combination for Pancreatic Cancer Therapy

Personalized Immunotherapy; Novel Approaches, Targets, and Therapeutics

Andrew Lowy, MD (UC San Diego)

Yuan Chen, PhD (UC San Diego)

Outcomes for pancreatic duct adenocarcinoma (PDAC) patients remain poor by any reasonable metric and thus more effective therapies are needed. We hypothesize that targeting the post translational modification, SUMOylation, will be an effective therapy for PDAC as we have shown SUMO inhibition (SUMOi) activates anti-PDAC immune responses. More recently we have found that SUMOi synergizes with chemotherapeutic agents used to treat PDAC most notably, irinotecan. In this proposal, we will determine the mechanism underlying this synergy and the effectiveness of combining SUMOi with both irinotecan and other immunomodulatory agents in murine and human models of the disease. Given the availability of recent development of clinical grade SUMOi’s and that irinotecan is part of approved first and second-line therapies for PDAC, we believe the results of our studies will provide sufficient rationale to move these strategies directly to the clinic for the treatment of PDAC patients