Both HIF-1α and HIF-2α are associated with tumor aggressiveness; HIF-1α promotes the phenotype and function of CSCs, whereas HIF-2α is highly expressed in CSCs; also known as TIC of neuroblastoma, glioblastoma, renal cell carcinoma, and breast carcinoma are associated with unfavorable disease outcome [24]. Here, EPAS1 is linked to hereditary clear cell renal cell carcinoma.