EPAS1 and nonpapillary renal cell carcinoma: Preclinical studies have shown that HIF-2α antagonists are capable of inhibiting tumor growth in several models of renal cancer, and clinical trials of the first-in-class HIF-2α antagonist PT2385 [(S)-3-((2,2-difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzonitrile] have achieved promising results in ccRCC [116].