1. ¹Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, New York, NY 10591, USA
2. ²Herbert Irving Comprehensive Cancer Center, Columbia University, 1130 St Nicholas Avenue, New York, NY 10032, USA

Correspondence: Dr G Thurston, E-mail: Gavin.Thurston@regeneron.com; J Kitajewski, E-mail: jkk9@columbia.edu

Received 20 December 2007; Revised 5 June 2008; Accepted 6 June 2008; Published online 30 September 2008.

Abstract

Tumour angiogenesis has become an important target for antitumour therapy, with most current therapies aimed at blocking the VEGF pathway. However, not all tumours are responsive to VEGF blockers, and some tumours that are responsive initially may become resistant during the course of treatment, thus there is a need to explore other angiogenesis signalling pathways. Recently, the Delta-Notch pathway, and particularly the ligand Delta-like 4 (Dll4), was identified as a new target in tumour angiogenesis. An important feature in angiogenesis is the manifold ways in which the VEGF and Delta-Notch pathways interact. The emerging picture is that the VEGF pathway acts as a potent upstream activating stimulus for angiogenesis, whereas Delta-Notch helps to guide cell fate decisions that appropriately shape the activation. Here we review the two signalling pathways and what is currently known about the ways in which they interact during tumour angiogenesis.