Since our genetic experiments demonstrated that HIF-1α is necessary for the efficient initiation of ccRCC formation we wondered firstly if HIF-1α is generally required for cellular proliferation following loss of Vhl and secondly whether established Vhl∆/∆Trp53∆/∆Rb1∆/∆ tumours remain dependent on HIF-1α or whether they might lose this dependency during tumour evolution. The gene discussed is HIF1A; the disease is neoplasm.