Pre-clinical studies pointed out the synergistic nature of targeting the PI3K/AKT pathway in combination with either BRAF or MEK inhibitors [35,60] and Phase I/II trials are evaluating such combination regimens in patients (Table 2): preliminary data show that these combinations are tolerated and active in patients with BRAF-mutated metastatic melanoma [9]. The gene discussed is PIK3CA; the disease is metastatic melanoma.