EPAS1 and nonpapillary renal cell carcinoma: We also confirmed that preventing the downregulation of CCND1 with two different CCND1 CRISPRa sgRNAs (Fig. 2A–H; Supplementary Fig. S5A–S5D), or by exogenous CCND1 expression driven by a constitutive promoter (Fig. 3A–H; Supplementary Fig. S6A–S6D), rendered ccRCC lines largely resistant to PT2399 and to CRISPR-mediated elimination of HIF2α.