In support of this approach, reports show that in vivo endothelial HIF1α or HIF2α deficiency resulted in enhanced tumor necrosis due to lack of nutrients with consequent reduction in tumor growth and number of tumor vessels [66,69]; in contrast, heterozygous deficiency of PHD2 restored tumor oxygenation and endothelial normalization, inhibiting metastasis [158]. This evidence concerns the gene EPAS1 and neoplasm.