Tumour targeting by microtubule-depolymerizing vascular disrupting agents.
Low molecular weight vascular disrupting agents of the microtubule depolymerizing family cause marked and selective disruption of the established tumour blood vessel network, resulting in tumour cell necrosis. The combretastatins are members of this family and these, together with several other related compounds, have undergone extensive preclinical testing and are now in clinical trials for cancer. Potentially, vascular disrupting agents can also interfere with angiogenesis and constitute a very promising group of novel cancer drugs. In vitro analysis of their signalling activities points to the endothelial cytoskeleton as being their major target and a key player in the events that culminate in vascular collapse. As more of these agents progress into the clinical setting, more research in this area is warranted in order to decipher exact mechanisms responsible for vascular disruption and to understand the reasons for drug selectivity for the tumour vasculature. This information is essential in order to identify new targets within the tumour vasculature and to improve present therapies.
Kanthou
Chryso
C
University of Sheffield, Cancer Research UK, Tumour Microcirculation Group, School of Medicine & Biomedical Sciences, Beech Hill Road, Sheffi eld, S10 2RX, UK. C.Kanthou@sheffi eld.ac.uk
Tozer
Gillian M
GM
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D013267:Stilbenes / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C058728:fosbretabulin