Review
Cancer Gene Therapy (2009) 16, 541–550; doi:10.1038/cgt.2009.25; published online 3 April 2009
Development of gene therapy in association with clinically used cytotoxic deoxynucleoside analogues
C Hébrard1,2, C Dumontet1,2 and L P Jordheim1,2
- 1Université de Lyon, Lyon, France
- 2INSERM U590, Lyon, France
Correspondence: Dr LP Jordheim, Laboratoire de Cytologie Analytique – INSERM U590, Faculté de Médecine Rockefeller, 8, Avenue Rockefeller, 69008 Lyon, France. E-mail: jordheim@yahoo.com
Received 25 October 2008; Revised 2 December 2008; Accepted 24 January 2009; Published online 3 April 2009.
Abstract
The clinical use of cytotoxic deoxynucleoside analogues is often limited by resistance mechanisms due to enzymatic deficiency, or high toxicity in nontumor tissues. To improve the use of these drugs, gene therapy approaches have been proposed and studied, associating clinically used deoxynucleoside analogues such as araC and gemcitabine and suicide genes or myeloprotective genes. In this review, we provide an update of recent results in this area, with particular emphasis on human deoxycytidine kinase, the deoxyribonucleoside kinase from Drosophila melanogaster, purine nucleoside phosphorylase from Escherichia coli, and human cytidine deaminase. Data from literature clearly show the feasibility of these systems, and clinical trials are warranted to conclude on their use in the treatment of cancer patients.
Keywords:
suicide gene, deoxynucleoside analogues, dCK, Dm-dNK, cytidine deaminase, PNP
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