It is widely accepted that metastasis originates from CSCs with tumor-initiating capabilities that allow most disseminated tumor cells to reconstitute growing, heterogeneous secondary tumors.89 Blocking HIF-1α or HIF-2α activity results in dramatically decreased CSC proliferation and self-renewal in hematological malignancies and glioma stem cells.40, 90, 91, 92 Limited research has indicated that HIF-2α also plays roles in metastasis of digestive tract cancers by regulating the CSCs. The gene discussed is EPAS1; the disease is central nervous system cancer.