Vascular damaging agents.

To provide a comprehensive overview on vascular targeting agents and the application of radiobiological principles in pre-clinical and clinical studies, we completed a comprehensive review of published medical studies on vascular targeting agents using Pub Med. Vascular targeting agents are now divided into vascular disrupting agents (VDAs), which target the pre-existing tumour vasculature, and angiogenesis inhibitors (AIs), which prevent the formation of new blood vessels. Modest success has been seen when VDAs and AIs are used as single agents and therefore combination therapies that can work in a complimentary and synergistic manner, targeting both the tumour cells and endothelial cells, are needed. Radiobiological principles have been used to increase our understanding of these agents, and can explain the increased efficacy of combination treatments. In particular, the alteration of the tumour microenvironment by AIs and VDAs can lead to enhanced efficacy when combined with chemotherapy or radiotherapy, with phase II/III trials showing encouraging results. The optimal use and scheduling of AIs and VDAs remains to be determined. Further understanding of the mechanisms of action of these potentially very exciting anti-neoplastic agents is urgently required.