Tumour targeting by microtubule-depolymerising vascular disrupting agents

Abstract

Low molecular weight vascular disrupting agents of the microtubule depolymerising 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.

Keywords::

• angiogenesis
• combretastatins
• cytoskeleton
• endothelial cells
• microtubule depolymerising agents
• mitogen activated protein kinases
• Rho-GTPases
• microtubules
• vascular disrupting agents

Notes