BRAF Inhibitor Resistance Confers Increased Sensitivity to Mitotic Inhibitors.

ABSTRACT: Single agent and combination therapy with BRAF^V600E/K and MEK inhibitors have remarkable efficacy against melanoma tumors with activating BRAF mutations, but in most cases BRAF inhibitor (BRAFi) resistance eventually develops. One resistance mechanism is reactivation of the ERK pathway. However, only about half of BRAFi resistance is due to ERK reactivation. The purpose of this study is to uncover pharmacological vulnerabilities of BRAFi-resistant melanoma cells, with the goal of identifying new therapeutic options for patients whose tumors have developed resistance to BRAFi/MEKi therapy. We screened a well-annotated compound library against a panel of isogenic pairs of parental and BRAFi-resistant melanoma cell lines to identify classes of compounds that selectively target BRAF

SUBMITTER: Misek SA 

PROVIDER: S-EPMC9015667 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature