Abstract B143: Functional screening of Arid1a-deficient pancreatic adenocarcinoma using the MAPS platform
Wenjia Wang, Olivia Schmidt, Sara K. Blick-Nitko, Isaac S. Harris, Aram F. HezelAbstract
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Citation Format:
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.