Proof-of-principle that these approaches are likely to be tolerable and effective comes from previously reported therapeutic effects of Acriflavine, which inhibits the binding of both HIF-1α and HIF-2α to HIF-1β79,80, in the Vhl∆/∆Trp53∆/∆Rb1∆/∆ ccRCC model16, as well as in xenograft and autochthonous mouse models of several different types of tumours79,81–83. This evidence concerns the gene EPAS1 and nonpapillary renal cell carcinoma.