Importantly, recent findings have also indicated that HIF-1α and HIF-2α play critical roles for the gain of more malignant phenotypes by highly tumourigenic cancer stem/progenitor cells endowed with stem cell-like properties also designated as cancer-, tumour-, and metastasis-initiating cells that are able to generate the bulk mass of heterogeneous and differentiated cancer cells within tumours and which are involved in primary cancer progression, metastases, resistance to current cancer therapies and disease relapse [14, 45–53]. Here, EPAS1 is linked to neoplasm.