VHL and cancer: In ccRCC cells, the pseudohypoxic state following HIF activation due to loss of VHL results in a shift from mitochondrial to glycolytic metabolism.21 Recently, a significant difference in the metabolic profile of ccRCC compared with other investigated tumor types was described.10 Even though the Warburg effect is seen in many cancer forms, ccRCC seems to be uniquely dependent on glycolysis, showing a reduction of most other energy-generating metabolic processes.