Finally, the emerging relationships among hypoxia, HIF-2α and SERPINB3 become particularly intriguing on the basis of the proposed hypothesis of a switch from HIF-1 to HIF-2 (and then from HIF-1α to HIF-2α) - dependent transcription during chronic hypoxia in solid tumors, favoring involvement of cancer stem cells and promoting inhibition of apoptosis, induction of cell proliferation and invasiveness/metastasis [47,48]. This evidence concerns the gene EPAS1 and cancer.