EPAS1 and nonpapillary renal cell carcinoma: Several lines of evidence demonstrate that HIF-2α is the primary oncogenic driver in ccRCC.6, 7, 8 In addition, HIF-2α predominantly regulates angiogenic genes such as VEGF in this tumor type.9, 10, 11 In contrast, recent evidence suggests that HIF-1α acts as a tumor suppressor in ccRCC.10, 12 ccRCC is also highly resistant to chemotherapy and radiotherapy and some studies have shown that this resistance can be circumvented by inhibition of HIF-2α.