The tumor suppressor von Hippel-Lindau (VHL) gene is one of the most important suppressors of the HIF2α/VEGF pathway and 45% of metastatic RCC present the mutant or lost VHL gene [58], which might lead to constitutively activated HIF-VEGF signals to induce the RCC progression [59,60]. Here, EPAS1 is linked to renal cell carcinoma.