Abstract B143: Functional screening of Arid1a-deficient pancreatic adenocarcinoma using the MAPS platform
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited therapeutic options. Approximately one-third of PDAC tumors harbor alterations in chromatin-remodeling genes, including loss-of-function mutations in ARID1A occurring in approximately 8% of cases. However, actionable vulnerabilities associated with ARID1A deficiency remain poorly defined. We hypothesized that ARID1A loss creates targetable cellular dependencies that can be identified through functional pharmacologic screening. We utilized the Multifunctional Approach to Pharmacologic Screening (MAPS) platform to compare drug responses in murine PDAC cell lines derived from genetically engineered mouse models with deleted or wild-type Arid1a. MAPS enables high-throughput screening of compounds across ten serial dilutions, allowing quantitative assessment of differential drug sensitivity. The screening library includes FDA-approved agents that have established in vivo profiles and safety data to facilitate the translational potential of identified therapeutic candidates. Comparative screening identified distinct drug sensitivity patterns between Arid1a-null and Arid1a-wildtype PDAC cells, supporting altered pathway dependencies associated with Arid1a loss. Notably, Arid1a-null cells demonstrated increased sensitivity to compounds targeting redox homeostasis and purine synthesis. The MAPS platform identified candidate therapeutic vulnerabilities associated with Arid1a deficiency in PDAC. These findings provide a rationale for mechanistic studies and validation of candidate targets to support the development of precision therapeutic strategies for patients with ARID1A-mutant PDAC. Wenjia Wang, Olivia Schmidt, Sara K. Blick-Nitko, Isaac S. Harris, Aram F. Hezel. Functional screening of Arid1a-deficient pancreatic adenocarcinoma using the MAPS platform [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr B143.