While HIF-1α has been perceived in the past to act as tumor suppressor in advanced ccRCC [1], we recently demonstrated its crucial driver role in ccRCC formation [2], at least in the setting of the autochthonous ccRCC mouse model driven by deletion of Vhl, Trp53, and Rb1, arguing that HIF-1α inhibition should also be considered as a new ccRCC therapeutic concept in at least some settings. Here, RB1 is linked to neoplasm.