We discovered that failure to downregulate cyclin D1 abrogates the antiproliferative effects of HIF2 inhibitors in ccRCC cells in cell culture and, in conjunction with maintenance of VEGF expression, in nude mice orthotopic xenografts assays and that the proproliferative effects of cyclin D1 require that it activate the CDK4 and/or CDK6 kinases. This evidence concerns the gene CCND1 and nonpapillary renal cell carcinoma.