ccRCC exemplifies this complexity: HIF-2α stabilization induces glycolysis via pyruvate dehydrogenase kinase (PDK)-mediated suppression of oxidative phosphorylation (OXPHOS), while simultaneously upregulating glutamine transporters to fuel reductive carboxylation—a metabolic bypass sustaining lipid biosynthesis under hypoxia [19, 20]. This evidence concerns the gene EPAS1 and nonpapillary renal cell carcinoma.