title: Dll4-Notch signaling as a therapeutic target in tumor angiogenesis.
abstract: Tumor angiogenesis is an important target for cancer therapy, with most current therapies designed to block the VEGF signaling pathway. However, clinical resistance to anti-VEGF therapy highlights the need for targeting additional tumor angiogenesis signaling pathways. The endothelial Notch ligand Dll4 (delta-like 4) has recently emerged as a critical regulator of tumor angiogenesis and thus as a promising new therapeutic anti-angiogenesis target. Blockade of Dll4-Notch signaling in tumors results in excessive, non-productive angiogenesis with resultant inhibitory effects on tumor growth, even in some tumors that are resistant to anti-VEGF therapies. As Dll4 inhibitors are entering clinical cancer trials, this review aims to provide current perspectives on the function of the Dll4-Notch signaling axis during tumor angiogenesis and as a target for anti-angiogenic cancer therapy.
authors.affiliation: Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. Gavin.Thurston@regeneron.com.
authors.forename: Frank
authors.initials: F
authors.lastname: Kuhnert
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Kirshner
authors.forename: Gavin
authors.initials: G
authors.lastname: Thurston