Over the past few years, a vertical combination of BRAF and MEK inhibitors (dabrafenib/trametinib or vemurafenib/cobimetinib) has demonstrated striking clinical efficacy and has become a standard of care in patients with BRAF-mut melanoma and lung cancer [13–16], although the molecular mechanisms by which combined BRAF/MEK inhibition results in synergistic anti-tumor activity are still not completely clear and the same combinations have not met with the same therapeutic success in other BRAF-mut cancer type of different histological origin [17]. This evidence concerns the gene BRAF and cancer.