However, these inhibitors were designed to inhibit HIF2α transcriptional activity and could only inhibit the ccRCC progression in certain preclinical models [15, 16], and the only approved such drug Belzutifan (PT2977) with only an overall response rate of 49% (95% CI: 36–62) in VHL mutant ccRCC [17]. Here, VHL is linked to nonpapillary renal cell carcinoma.