Increased inflammatory lipid metabolism and anaplerotic mitochondrial activation follow acquired resistance to vemurafenib in BRAF-mutant melanoma cells.

ABSTRACT:

Background

BRAF inhibitors, such as vemurafenib, have shown efficacy in BRAF-mutant melanoma treatment but acquired-resistance invariably develops. Unveiling the potential vulnerabilities associated with vemurafenib resistance could provide rational strategies for combinatorial treatment.

Methods

This work investigates the metabolic characteristics and vulnerabilities of acquired resistance to vemurafenib in three generated BRAF-mutant human melanoma cell clones, analysing metabolic profiles, gene and protein expression in baseline and nutrient withdrawal conditions. Preclinical findings are correlated with gene expression analysis from publicly available clinical datasets.

Results

Two vemurafenib-resistant clones showed dependency on lipid metabolism and increased pr

SUBMITTER: Delgado-Goni T 

PROVIDER: S-EPMC6964672 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature