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Published on: September 5, 2016
Development of gene therapy in association with clinically used cytotoxic deoxynucleoside analogues
C Hébrard1, C Dumontet, L P Jordheim
1Université de Lyon, Lyon, France.
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.
Insights
Gene therapy combining deoxynucleoside analogues with suicide or myeloprotective genes shows promise for cancer treatment. Further clinical trials are needed to confirm the efficacy and safety of these innovative gene therapy approaches.
Area of Science:
- Oncology
- Gene Therapy
- Biochemistry
Background:
- Cytotoxic deoxynucleoside analogues face limitations in cancer therapy due to drug resistance and toxicity.
- Gene therapy offers a strategy to enhance the efficacy and safety of these agents.
Purpose of the Study:
- To review recent advancements in gene therapy for cancer, focusing on deoxynucleoside analogues.
- To highlight the role of specific enzymes and genes in these therapeutic strategies.
Main Methods:
- Review of current literature on gene therapy approaches in oncology.
- Analysis of studies involving deoxynucleoside analogues (e.g., araC, gemcitabine) combined with suicide or myeloprotective genes.
- Focus on key enzymes: human deoxycytidine kinase, Drosophila melanogaster deoxyribonucleoside kinase, E. coli purine nucleoside phosphorylase, and human cytidine deaminase.
Main Results:
- Gene therapy systems integrating deoxynucleoside analogues with therapeutic genes demonstrate feasibility.
- Specific enzymes play crucial roles in the activation or detoxification of these agents within gene therapy contexts.
Conclusions:
- Gene therapy approaches show significant potential for improving cancer treatment outcomes.
- Clinical trials are essential to validate the therapeutic benefits and safety of these gene-modified deoxynucleoside analogue systems in cancer patients.
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