Ceritinib Enhances the Efficacy of Trametinib in BRAF/NRAS-Wild-Type Melanoma Cell Lines.

ABSTRACT: Targeted therapy options are currently lacking for the heterogeneous population of patients whose melanomas lack BRAF or NRAS mutations (∼35% of cases). We undertook a chemical biology screen to identify potential novel drug targets for this understudied group of tumors. Screening a panel of 8 BRAF/NRAS-WT melanoma cell lines against 240 targeted drugs identified ceritinib and trametinib as potential hits with single-agent activity. Ceritinib enhanced the efficacy of trametinib across the majority of the BRAF/NRAS-WT cell lines, and the combination showed increased cytotoxicity in both three-dimensional spheroid culture and long-term colony formation experiments. Coadministration of ceritinib and trametinib led to robust inhibition of tumor growth in an in vi

SUBMITTER: Verduzco D 

PROVIDER: S-EPMC5752595 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature