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Inhibiting tumor-associated angiogenesis is a validated major strategy in cancer therapy.New drug targets desired to be excavated for the poor response and resistance of the early antiangiogenic therapies.Recently, Dll4-Notch signaling pathway has emerged as a critical regulator of the development and maintenance of tumor angiogenesis.Delta-like ligand 4 (Dl14), the only Notch ligand to be selectively over-expressed on endothelial cells, is involved in tumor angiogenesis.Furthermore, Dll4 is a negative-feedback regulator of angiogenesis and strongly upregulated in tumor vasculature.