Several proangiogenic factors such as angiopoietin 2 (ANG-2), EGF, bFGF, keratinocyte growth factor, IGF-1, TGF-β, TNF-α and interleukins (IL-1, IL-8, IL-12 and IL-17) have been implicated in hypoxia-associated tumor refractoriness to anti-VEGFR therapy [184]. This evidence concerns the gene KDR and neoplasm.