EPAS1 and nonpapillary renal cell carcinoma: In mouse VHL–/– ccRCC xenograft experiments, silencing HIF2α using shRNAs or CRISPR/Cas9 suppresses tumor growth whereas forced production of HIF2α, such as through the expression of a non-hydroxylatable HIF2α mutant, bypasses pVHL’s tumor suppressor activity (28–32).