However, the VEGF/VEGFR signal is the primary target because the universal VHL loss in ccRCC, and the mTORC1, MET and IL–8, but not the EGFR or PI3K pathways are secondary targets based on the available clinical and preclinical studies in mRCC [4]. This evidence concerns the gene CXCL8 and nonpapillary renal cell carcinoma.