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Radiogenetic therapy: strategies to overcome tumor resistance

Radiogenetic therapy: strategies to overcome tumor resistance

Marples, B., Greco, O., Joiner, M.C. and Scott, S.D. (2003) Radiogenetic therapy: strategies to overcome tumor resistance. Current Pharmaceutical Design, 9 (26). pp. 2105-2112. ISSN 1381-6128 (Print), 1873-4286 (Online) (doi:10.2174/1381612033454090)

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Abstract

The aim of cancer gene therapy is to selectively kill malignant cells at the tumor site, by exploiting traits specific to cancer cells and / or solid tumors. Strategies that take advantage of biological features common to different tumor types are particularly promising, since they have wide clinical applicability. Much attention has focused on genetic methods that complement radiotherapy, the principal treatment modality, or that exploit hypoxia, the most ubiquitous characteristic of most solid cancers. The goal of this review is to highlight two promising gene therapy methods developed specifically to target the tumor volume that can be readily used in combination with radiotherapy. The first approach uses radiation-responsive gene promoters to control the selective expression of a suicide gene (e.g., herpes simplex virus thymidine kinase) to irradiated tissue only, leading to targeted cell killing in the presence of a prodrug (e.g., ganciclovir). The second method utilizes oxygen-dependent promoters to produce selective therapeutic gene expression and prodrug activation in hypoxic cells, which are refractive to conventional radiotherapy. Further refining of tumor targeting can be achieved by combining radiation and hypoxia responsive elements in chimeric promoters activated by either and dual stimuli. The in vitro and in vivo studies described in this review suggest that the combination of gene therapy and radiotherapy protocols has potential for use in cancer care, particularly in cases currently refractory to treatment as a result of inherent or hypoxia-mediated radioresistance.

Item Type: Article
Uncontrolled Keywords: radiation, gene therapy, hypoxia, carg elements, hre, gdept
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Faculty / Department / Research Group: Faculty of Engineering & Science > Medway School of Pharmacy
Faculty of Engineering & Science
Related URLs:
Last Modified: 14 Jul 2015 16:41
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
URI: http://gala.gre.ac.uk/id/eprint/8471

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