VHL and metabolic disease: RCC is a metabolic disease characterized by dysregulation of metabolic pathways involved in oxygen sensing (changes in the VHL/HIF pathway and subsequent upregulation of HIF response genes such as VEGF, PDGF, and EGF), energy sensing (succinate dehydrogenase-deficient RCC), and/or nutrient-sensing cascades (dysregulation of the AMPK-mTOR and PI3K-AKT pathways).