Some of the subclonal genetic perturbations, such as gain-of-function mutation in NRAS, MEK1/MEK2 and PI3K or gene amplification of microphthalmia-associated transcription factor (MITF) offer alternative paths that allow tumor cells to overcome their addiction to constitutive activation of BRAF and bypass the blockade of this specific signal transduction route, endowing them with resistance to BRAF inhibitors [17,18]. This evidence concerns the gene BRAF and neoplasm.