Concurrent HER or PI3K Inhibition Potentiates the Antitumor Effect of the ERK Inhibitor Ulixertinib in Preclinical Pancreatic Cancer Models.

ABSTRACT: Effective treatment for pancreatic ductal adenocarcinoma (PDAC) is an urgent, unmet medical need. Targeting KRAS, the oncogene that is present in >95% of PDAC, is a heavily pursued strategy, but remains unsuccessful in the clinic. Therefore, targeting key effector cascades of KRAS oncoprotein, particularly the mitogenic RAF-MEK-ERK pathway, represents the next best strategy. However, RAF or MEK inhibitors have failed to show clinical efficacy in PDAC. Several studies have shown that cancer cells treated with RAF or MEK inhibitors adopt multiple mechanisms to reactivate ERK signaling. Therefore, development of ERK-specific inhibitors carries the promise to effectively abrogate this pathway. Ulixertinib (or BVD-523) is a first-in-class ERK-specific inhibitor that has demonstrated prom

SUBMITTER: Jiang H 

PROVIDER: S-EPMC6168412 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature