Cyclooxygenase-2 Influences Response to Cotargeting of MEK and CDK4/6 in a Subpopulation of Pancreatic Cancers.

ABSTRACT: The ineffectiveness of chemotherapy in patients with pancreatic cancer highlights a critical unmet need in pancreatic cancer therapy. Two commonly mutated genes in pancreatic cancer, KRAS and CDKN2A, have an incidence exceeding 90%, supporting investigation of dual targeting of MEK and CDK4/6 as a potential therapeutic strategy for this patient population. An in vitro proliferation synergy screen was conducted to evaluate response of a panel of high passage and patient-derived pancreatic cancer models to the combination of trametinib and palbociclib to inhibit MEK and CDK4/6, respectively. Two adenosquamous carcinoma models, L3.6pl and UM59, stood out for their high synergy response. In vivo studies confirmed that this combination treatment approach was highly e

SUBMITTER: Maust JD 

PROVIDER: S-EPMC6279520 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature