Abstract 2418 Dual Inhibition of PRMT5 and CHK1 Drives Cell Cycle Arrest, Transcriptional Reprogramming, and Apoptosis in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States, with a dismal 5-year survival rate of only 13%. Despite advances in cancer therapies, survival outcomes for PDAC patients have seen only marginal improvements, highlighting an urgent need for innovative therapies. Protein arginine methyltransferase 5 (PRMT5) has emerged as a promising therapeutic target, with ongoing clinical trials for PDAC treatment. Here, we aimed to define the impact of PRMT5 inhibition on DDR signaling and related processes in PDAC, highlighting vulnerabilities to inform novel combination therapies.