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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