Combination of the MTA-Cooperative PRMT5 Inhibitor BMS-986504 and KRAS Inhibitors Is an Effective Treatment Strategy for MTAP-Deleted KRAS-Mutant Pancreatic Cancer.

doi:10.1158/0008-5472.CAN-25-1507

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Combination of the MTA-Cooperative PRMT5 Inhibitor BMS-986504 and KRAS Inhibitors Is an Effective Treatment Strategy for MTAP-Deleted KRAS-Mutant Pancreatic Cancer.

Cancer research - 15 Sept 2025

Drizyte-Miller Kristina, Engstrom Lars D, Klomp Jeffrey A, Stalnecker Clint A, Stamey Addison G, Taylor Khalilah E, Roach Mallory K, Robb Ryan, Waters Laura M, Calinisan Andrew, Degan Seamus, Chang Wen-Hsuan, Helu Xousaen M, Nguyen David, Baldelli Elisa, Pierobon Mariaelena, Petricoin Emanuel F, Briere David M, Hallin Jill, Christensen James G, Bryant Kirsten L, Cox Adrienne D, Olson Peter, Der Channing J

Abstract excerpt

Protein arginine methyltransferase 5 (PRMT5) is a synthetic lethal target in MTAP-deleted (MTAP-del) cancers. The MTA-cooperative PRMT5 inhibitor BMS-986504 exhibited potent and selective antitumor activity in MTAP-del preclinical models and demonstrated activity in MTAP-del patients without the toxicity associated with previous PRMT5 inhibitors. In this study, we focused on pancreatic ductal adenocarcinoma...

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Identifiers

PMID: 40694535
DOI: 10.1158/0008-5472.CAN-25-1507
PMCID: PMC12717533

Genes

MTAP
PRMT5
KRAS

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