Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma.

ABSTRACT: Genomic diversity among melanoma tumors limits durable control with conventional and targeted therapies. Nevertheless, pathologic activation of the ERK1/2 pathway is a linchpin tumorigenic mechanism associated with the majority of primary and recurrent disease. Therefore, we sought to identify therapeutic targets that are selectively required for tumorigenicity in the presence of pathologic ERK1/2 signaling. By integration of multigenome chemical and genetic screens, recurrent architectural variants in melanoma tumor genomes, and patient outcome data, we identified two mechanistic subtypes of BRAF^V600 melanoma that inform new cancer cell biology and offer new therapeutic opportunities. Subtype membership defines sensitivity to clinical MEK inhibitors versus TBK1/IKBKε inhibitors

SUBMITTER: Eskiocak B 

PROVIDER: S-EPMC5540806 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature