Open AccessResistance to BRAF inhibitors induces glutamine dependency in melanoma cells
Author(s) -
Baenke Franziska,
Chaneton Barbara,
Smith Matthew,
Van Den Broek Niels,
Hogan Kate,
Tang Haoran,
Viros Amaya,
Martin Matthew,
Galbraith Laura,
Girotti Maria R.,
Dhomen Nathalie,
Gottlieb Eyal,
Marais Richard
Publication year - 2016
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2015.08.003
Subject(s) - glutaminolysis , glutamine , melanoma , cancer research , biology , mitochondrion , metabolism , oxidative phosphorylation , biochemistry , amino acid
BRAF inhibitors can extend progression‐free and overall survival in melanoma patients whose tumors harbor mutations in BRAF. However, the majority of patients eventually develop resistance to these drugs. Here we show that BRAF mutant melanoma cells that have developed acquired resistance to BRAF inhibitors display increased oxidative metabolism and increased dependency on mitochondria for survival. Intriguingly, the increased oxidative metabolism is associated with a switch from glucose to glutamine metabolism and an increased dependence on glutamine over glucose for proliferation. We show that the resistant cells are more sensitive to mitochondrial poisons and to inhibitors of glutaminolysis, suggesting that targeting specific metabolic pathways may offer exciting therapeutic opportunities to treat resistant tumors, or to delay emergence of resistance in the first‐line setting.