DECIPHERING THE METABOLIC VULNERABILITY OF MALIGNANT MELANOMA CELLS

ARBE, MARÍA FLORENCIA; KRASNAPOLSKY, M; GLIKIN, GERARDO C; FINOCCHIARO, L. M. E; VILLAVERDE M. S.

Congreso; SAIC 2021; 2021

Aggressive melanoma is still a highly live-threatening malignancybeing BRAF mutation its most frequent oncogenic driver follow byNRAS mutation. In addition, metabolic rewiring has been involvedin progression and resistance of melanoma. Here we studied theresponse of eight human malignant melanoma cell lines treated atdifferent levels of key metabolic pathways to address their vulnerability and to interpretate their response in terms of the metabolic andgenetic background of each cell line. We found that melanoma cellsexhibited a broad spectrum of sensitivities to bioenergetic modulators. Based on a previous published work, we defined a concentration for each modulator to segregate melanoma cells as sensitive(considered as some dependency on this pathway) or non-sensitive.After that, we found that the order of response to metabolic modulators was BRAFV600R≥BRAFV600E>NRASQ61K. In addition,we found a significant positive correlation between the response toDCA (Pyruvate dehydrogenase inhibitor) vs RAD001 (mTORC1 inhibitor) (r=0.87; p