Metastatic RCC (mRCC) was considered refractory to systemic therapy for many years, but there are now seven so called “targeted” agents approved for this condition, which target the critical vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways, leading to inhibition of angiogenesis and cell survival and proliferation. This evidence concerns the gene VEGFA and renal cell carcinoma.