Gene therapy targeting to tumor endothelium

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. Access through your

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BEING VIEWED BY OTHERS TARGETING THE TUMOUR VASCULATURE: FROM VESSEL DESTRUCTION TO PROMOTION Article 29 August 2024 MILESTONES IN TUMOR VASCULARIZATION AND ITS THERAPEUTIC TARGETING Article

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ACKNOWLEDGEMENTS We acknowledge the support of the Clarendon Fund and Balliol College, University of Oxford and the Consejo Nacional de Ciencia y Tecnologia (CONACYT) (MBP), Cancer Research

UK (ALH) and the National Translational Cancer Research Network (LWS). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Clinical Pharmacology, University of Oxford, Radcliffe

Infirmary, Oxford,, UK M Bazan-Peregrino & L W Seymour * Cancer Research UK Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford,,

UK A L Harris Authors * M Bazan-Peregrino View author publications You can also search for this author inPubMed Google Scholar * L W Seymour View author publications You can also search for

this author inPubMed Google Scholar * A L Harris View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to L W Seymour.

RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Bazan-Peregrino, M., Seymour, L. & Harris, A. Gene therapy targeting to tumor endothelium. _Cancer

Gene Ther_ 14, 117–127 (2007). https://doi.org/10.1038/sj.cgt.7701001 Download citation * Received: 13 October 2005 * Revised: 19 May 2006 * Accepted: 22 July 2006 * Published: 10 November

2006 * Issue Date: 01 February 2007 * DOI: https://doi.org/10.1038/sj.cgt.7701001 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable

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* targeting * angiogenesis