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dc.contributor.authorBaenke, Franziskaen
dc.contributor.authorChaneton, Ben
dc.contributor.authorSmith, Matthewen
dc.contributor.authorVan Den Broek, Nen
dc.contributor.authorHogan, Kateen
dc.contributor.authorTang, Haoranen
dc.contributor.authorViros, Amayaen
dc.contributor.authorMartin, Matthewen
dc.contributor.authorGalbraith, Len
dc.contributor.authorGirotti, Maria Rominaen
dc.contributor.authorDhomen, Nathalieen
dc.contributor.authorGottlieb, Een
dc.contributor.authorMarais, Richarden
dc.date.accessioned2015-10-26T10:48:21Zen
dc.date.available2015-10-26T10:48:21Zen
dc.date.issued2015-08-20en
dc.identifier.citationResistance to BRAF inhibitors induces glutamine dependency in melanoma cells. 2015: Mol Oncolen
dc.identifier.issn1878-0261en
dc.identifier.pmid26365896en
dc.identifier.doi10.1016/j.molonc.2015.08.003en
dc.identifier.urihttp://hdl.handle.net/10541/581104en
dc.description.abstractBRAF 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.
dc.languageENGen
dc.language.isoenen
dc.rightsArchived with thanks to Molecular oncologyen
dc.titleResistance to BRAF inhibitors induces glutamine dependency in melanoma cells.en
dc.typeArticleen
dc.contributor.departmentMolecular Oncology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow Road, Manchester M20 4BX,en
dc.identifier.journalMolecular Oncologyen
html.description.abstractBRAF 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.


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