To investigate the role of hypoxia and drug resistance in the response of renal cancer cells to sunitinib, CAKI-1 cells carrying wild-type VHL and low basal expression of HIF-1α, HIF-2α and CA9 (Figure 2A), and 786–0 cells carrying mutated VHL, low basal HIF- 1α expression and high HIF-2α and CA9 protein levels were used to develop sunitinib resistant cell lines. This evidence concerns the gene EPAS1 and renal carcinoma.