AKT1 and cutaneous melanoma: Although RAS signaling acts upstream of both MAPK and PI3K/AKT signaling (Cox & Der, 2010), it is interesting to note that the two main NRAS activating mutations in cutaneous melanoma, the hotspots Q61 (80% of NRAS subtype tumors) and G12 (15%), drive a differential activation of the downstream pathways with preferential activation of MAPK or PI3K/AKT, respectively, suggesting a complex modulation of the structure and activity of oncogenic proteins (Posch et al, 2016).