Transposon mediated functional genomic screening for BRAF inhibitor resistance reveals convergent Hippo and MAPK pathway activation events.

ABSTRACT: Genotype-informed anticancer therapies such as BRAF inhibitors can show remarkable clinical efficacy in BRAF-mutant melanoma; however, drug resistance poses a major hurdle to successful cancer treatment. Many resistance events to targeted therapies have been identified, suggesting a complex path to improve therapeutics. Here, we showed the utility of a piggyBac transposon activation mutagenesis screen for the efficient identification of genes that are resistant to BRAF inhibition in melanoma. Although several forward genetic screens performed in the same context have identified a broad range of resistance genes that poorly overlap, an integrative analysis revealed a much smaller functional diversity of resistance mechanisms, including reactivation of the MAPK pathway, PI3K-AKT pathway, and

SUBMITTER: Chen L 

PROVIDER: S-EPMC11760944 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature