Model of the BET and MEK inhibitor combination therapy to treat melanoma with NRAS mutation and immune therapy resistance Model of the BET and MEK inhibitor.

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Model of the BET and MEK inhibitor combination therapy to treat melanoma with NRAS mutation and immune therapy resistance Model of the BET and MEK inhibitor combination therapy to treat melanoma with NRAS mutation and immune therapy resistance (A) NRAS mutation constitutively activates RAF/MEK/ERK, PI3K/AKT, and Ral GEF/Ral A‐B signaling pathways and leads to BRD4 and TCF19 upregulation. The combination therapy of BET and MEK inhibitors reduces BRD4 and TCF19 expressions, which causes apoptosis of tumor cells. (B) Treatment with BRAF/MEK inhibitors or immune therapy targeting immune checkpoints (anti‐PD1 and anti‐CTLA4) shows excellent promises in melanoma only for a few cases, while melanomas with elevated TCF19 protein resist the treatment. A combined therapy of BET and MEK inhibitors causes cell cycle arrest and apoptosis through inhibition of TCF19. Yanlin Yu EMBO Mol Med. 2018;10:e8573 © as stated in the article, figure or figure legend