Activation of the RAS/BRAF/MAPK cascade, driver event in melanoma, can engage mTORC1 signaling via multiple mechanisms, including the activation of PI3K/Akt signaling downstream of RAS, and direct inactivation of the GAP activity of TSC1/TSC2 complexes towards Rheb via ERK-dependent TSC2 phosphorylation [277,278,279] (Figure 3). This evidence concerns the gene PIK3CA and melanoma.