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BRAF inhibitor treatment causes melanoma cells to shift how they produce energy
Date:3/8/2013

elanoma cells suppresses oxidative phosphorylation by reducing expression of a transcription factor called MITF. Suppressing production of MITF reduced levels of a protein called PGC1α that regulates the generation and function of mitochondria. But melanoma cells treated with a BRAF inhibitor showed elevated MITF activity, along with increased expression of oxidative phosphorylation genes and greater numbers of mitochondria. By switching to oxidative phosphorylation to supply the energy they need, the tumor cells increased their ability to survive in spite of BRAF inhibitor treatment.

"These findings suggest that combination treatment with mitochondrial inhibitors could improve the efficacy of BRAF inhibitors in malignant melanoma," says Fisher, the Wigglesworth Professor of Dermatology at Harvard Medical School. "Several small molecules that target mitochondrial metabolism have been identified by investigators here at the MGH and elsewhere, and laboratory investigations of specific combinations of BRAF inhibitors with mitochondrial antagonists are currently underway."


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Contact: Michelle Marcella
mmarcella@partners.org
617-724-2755
Massachusetts General Hospital
Source:Eurekalert

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