EPAS1 and nonpapillary renal cell carcinoma: This greater potency of HIF-2α versus HIF-1α inhibition is an ideal combination for ccRCC since HIF-2α plays a central driving role in ccRCC progression and has limited expression in normal adult tissues, whereas HIF-1α, while also contributing to ccRCC progression, also plays a role in the homeostasis of some normal tissues [66].