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Abstract #2283

Metabolic profiling discriminates between BRAFi sensitive and BRAFi resistant melanoma cells

Stefania Acciardo1, Lionel Mignion1, Florian Gourgue1, Céline Schoonjans1, Nicolas Joudiou2, Bernard Gallez1, and Bénédicte F Jordan1

1Biomedical Magnetic Resonance Research Group, Université catholique de Louvain, Louvain Drug Research Institute, Brussels, Belgium, 2NEST Nuclear and Electron Spin Technologies Platform, Université catholique de Louvain, Louvain Drug Research Institute, Brussels, Belgium

The aim of this work is to identify a marker of response or resistance to BRAF inhibition in melanoma. BRAF inhibition resulted in a decrease of 13C label exchange between hyperpolarized [1-13C]pyruvate and lactate in sensitive, but not in resistant, melanoma cells. Such effect is likely to be mediated by a reduction of the lactate pool due to (i) decreased flux through glycolysis, (ii) reduced MCT1-mediated lactate uptake and (iii) increased lactate efflux via MCT4. The lactate/pyruvate ratio may help to discriminate between sensitive and resistant melanoma cells, by reflecting the different metabolic alterations that the cells undergo.

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