1. ¹Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, Oxford, UK
2. ²Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK

Correspondence: Professor LW Seymour, Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK. E-mail: len.seymour@clinical-pharmacology.oxford.ac.uk

Received 13 October 2005; Revised 19 May 2006; Accepted 22 July 2006; Published online 10 November 2006.

Abstract

Tumor-associated vasculature is a relatively accessible component of solid cancers that is essential for tumor survival and growth, providing a vulnerable target for cancer gene therapy administered by intravenous injection. Several features of tumor-associated vasculature are different from normal vasculature, including overexpression of receptors for angiogenic growth factors, markers of vasculogenesis, upregulation of coagulation cascades, aberrant expression of adhesion molecules and molecular consequences of hypoxia. Many of these differences provide candidate targets for tumor-selective 'transductional targeting' of genetically- or chemically modified vectors and upregulated gene expression can also enable 'transcriptional targeting', regulating tumor endothelia-selective expression of transgenes following nonspecific gene delivery. Tumor vasculature also represents an important site of therapeutic action by the secreted products of antiangiogenic gene therapies that are expressed in non-endothelial cells. In this review we assess the challenges faced and the vectors that may be suitable for gene delivery to exploit these targets. We also overview some of the strategies that have been developed to date and highlight the most promising areas of research.