Inter-Relationship Between Melanoma Vemurafenib Tolerance Thresholds and Metabolic Pathway Choice.

ABSTRACT: Melanomas quickly acquire resistance to vemurafenib, an important therapeutic for BRAFV600 mutant melanomas. Although combating vemurafenib resistance (VemR) to counter mitochondrial metabolic shift using mitochondria-targeting therapies has promise, no studies have analyzed the relationship between vemurafenib tolerance levels and metabolic plasticity. To determine how vemurafenib endurance levels drive metabolic plasticity, we developed isogenic BRAFV600E VemR melanoma models with variant vemurafenib tolerances and performed an integrative analysis of metabolomic and transcriptome alterations using metabolome, Mitoplate-S1, Seahorse, and RNA-seq assays. Regardless of drug tolerance differences, both VemR models display resistance to MEK inhibitor and sensitivity to Wnt/β-catenin inhibito

SUBMITTER: Nangia-Makker P 

PROVIDER: S-EPMC12191169 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature