BJR
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
British Journal of Radiology (2008) 81, S12-S20
© 2008 British Institute of Radiology
doi: 10.1259/bjr/36205483
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Tozer, G M
Right arrow Articles by Hill, S A
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tozer, G M
Right arrow Articles by Hill, S A
British Journal of Radiology 81 (2008),S12-S20 ©2008 The British Institute of Radiology

Full paper

Tumour vascular disrupting agents: combating treatment resistance

G M Tozer, PhD1, C Kanthou, PhD1, G Lewis2, V E Prise, BSc2, B Vojnovic, PhD2 and S A Hill, PhD2

1 University of Sheffield, Academic Unit of Surgical Oncology, K Floor, School of Medicine & Biomedical Sciences, Beech Hill Road, Sheffield S10 2RX, UK and 2 Oxford University Gray Cancer Institute, PO Box 100, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR, UK

Correspondence: Gillian M Tozer, University of Sheffield, Academic Unit of Surgical Oncology, K Floor, School of Medicine & Biomedical Sciences, Beech Hill Road, Sheffield S10 2RX, UK. E-mail: g.tozer{at}sheffield.ac.uk

A large group of tubulin-binding microtubule-depolymerizing agents act as tumour vascular disrupting agents (VDAs). Several members of this group are now in clinical trials in combination with conventional anticancer drugs and radiotherapy. Here we briefly update on the development of tubulin-binding combretastatins as VDAs, summarize what is known of their mechanisms of action and address issues relating to treatment resistance, using disodium combretastatin A-4 3–O-phosphate (CA-4-P) as an example. Characteristically, VDAs cause a rapid shutdown of blood flow to tumour tissue with much less effect in normal tissues. However, the tumour rim is relatively resistant to treatment. Hypoxia (or hypoxia reoxygenation) induces upregulation of genes associated with angiogenesis and drug resistance. It may be possible to take advantage of treatment-induced hypoxia by combining with drugs that are activated under hypoxic conditions. In summary, VDAs provide a novel approach to cancer treatment, which should effectively complement standard treatments, if treatment resistance is addressed by judicious combination treatment strategies.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
BJR DMFR IMAGING  ALL BIR JOURNALS 
Copyright © 2008 by the British Institute of Radiology.