KDR and neoplasm: In addition, Dll4/Notch signaling may mediate resistance to anti-VEGF therapy through multiple different mechanisms, e.g. decreased levels of hypoxia-induced VEGF and increased levels of the VEGF receptor VEGFR1 in the tumor stroma, decreased levels of VEGFR2 in large blood vessels, and reduced levels of VEGFR3 overall [54].