Although blocking one pathway might sensitize tumor vessels to inhibition of the other, much remains to be learned at the mechanistic levels as to how these two pathways interact during tumor vascularization; certainly not all of the above findings can be explained by a simple linear VEGF-Dll4-Notch4 feedback loop as described in the retinal angiogenesis model [20,22]. The gene discussed is NOTCH4; the disease is neoplasm.