Loading...
Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells.
Baenke, Franziska Chaneton, B Smith, Matthew Van Den Broek, N Hogan, Kate Tang, Haoran Viros, Amaya Martin, Matthew Galbraith, L Girotti, Maria Romina
Baenke, Franziska
Chaneton, B
Smith, Matthew
Van Den Broek, N
Hogan, Kate
Tang, Haoran
Viros, Amaya
Martin, Matthew
Galbraith, L
Girotti, Maria Romina
Citations
Altmetric:
Abstract
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.
Description
Date
2015-08-20
Publisher
Collections
Keywords
Type
Article
Citation
Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells. 2015: Mol Oncol