Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells

Baenke, F. et al. (2016) Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells. Molecular Oncology, 10(1), pp. 73-84. (doi: 10.1016/j.molonc.2015.08.003) (PMID:26365896) (PMCID:PMC4717845)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Chaneton, Miss Barbara and Gottlieb, Professor Eyal and Van Den Broek, Mr Niels and Galbraith, Dr Laura
• Authors: Baenke, F., Chaneton, B., Smith, M., Van Den Broek, N., Hogan, K., Tang, H., Viros, A., Martin, M., Galbraith, L., Girotti, M. R., Dhomen, N., Gottlieb, E., and Marais, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Molecular Oncology
• Publisher: Elsevier B.V
• ISSN: 1574-7891
• ISSN (Online): 1878-0261
• Published Online: 20 August 2015
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in Molecular Oncology 10(1):73-84
• Publisher Policy: Reproduced under a Creative Commons License