Disrupting tumour blood vessels.
Low-molecular-weight vascular-disrupting agents (VDAs) cause a pronounced shutdown in blood flow to solid tumours, resulting in extensive tumour-cell necrosis, while they leave the blood flow in normal tissues relatively intact. The largest group of VDAs is the tubulin-binding combretastatins, several of which are now being tested in clinical trials. DMXAA (5,6-dimethylxanthenone-4-acetic acid) - one of a structurally distinct group of drugs - is also being tested in clinical trials. A full understanding of the action of these and other VDAs will provide insights into mechanisms that control tumour blood flow and will be the basis for the development of new therapeutic drugs for targeting the established tumour vasculature for therapy.
Tozer
Gillian M
GM
Academic Unit of Surgical Oncology, Division of Clinical Sciences, University of Sheffield, Floor K, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK. g.tozer@sheffield.ac.uk
Kanthou
Chryso
C
Baguley
Bruce C
BC
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D001632:Bibenzyls / Q000494:pharmacology / Q000627:therapeutic use; D002199:Capillary Permeability; D002986:Clinical Trials as Topic; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use; D044004:Xanthones / Q000494:pharmacology / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D001632:Bibenzyls; D013267:Stilbenes; D044004:Xanthones; C066668:vadimezan; C040105:combretastatin