VHL and nonpapillary renal cell carcinoma: The inactivation of VHL in ccRCC leads to the aberrant accumulation of the transcription factors hypoxia-inducible factor (HIF)-1α and HIF-2α, despite normoxia with the resultant upregulation of pathways involved in glycolysis, fatty acid (FA), and glycogen synthesis [41,42,43] promoting a lactate-rich environment [34,44,45] (Table 1).