RET and renal cell carcinoma: Despite the failure of earlier attempts at combining VEGF/VEGFR- and mTOR-targeting agents, due to a mix of toxicity issues and lack of efficacy, a recent phase II randomized trial has established the combination of lenvatinib (an oral multitarget tyrosine kinase inhibitor of VEGFR-1, -2 and -3, with additional inhibitory activity against FGFR 1-4, PDGFRα, REarranged during Transfection (RET), and KIT) and everolimus, as one of the standards of care for the II-line treatment of advanced RCC [168,173,205,206].