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Progress in antiangiogenic gene therapy of cancer
1Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Background:
Because tumors require angiogenesis for growth, inhibiting angiogenesis is a promising strategy for treating cancer patients. Although numerous endogenous angiogenesis inhibitors have been discovered, the clinical evaluation of these agents has been hindered by high dose requirements, manufacturing constraints, and relative instability of the corresponding recombinant proteins. Therefore the delivery of these proteins using gene therapy has become increasingly attractive.
Methods:
Based on their own antiangiogenic gene therapy research, the authors evaluated the published experience with antiangiogenic gene therapy models using the National Library of Medicine's PubMed search service and the reference lists of the publications cited.
Results:
Greater than 40 endogenous inhibitors of angiogenesis have been characterized. Thirteen have been employed in gene therapy models, all of which showed antitumor activity in experimental animals. Other approaches have inhibited the expression or activity of proangiogenic cytokines such as vascular endothelial growth factor. The ideal gene delivery vector would target tumor tissue preferentially to minimize systemic toxicity of the transgene product. However, the low toxicity profile of endogenous inhibitors of angiogenesis has allowed the success of systemic antiangiogenic gene therapy in a number of preclinical models, in which normal host tissues act as a "factory" to produce high circulating concentrations of antiangiogenic proteins.
Conclusions:
Difficulties with the large-scale use of antiangiogenic agents have hindered their investigation in clinical trials. Antiangiogenic gene therapy offers the potential for cancer patients to manufacture their own antiangiogenic proteins. This strategy has been increasingly successful in preclinical models and represents an exciting new approach to cancer therapy.
Insights
Gene therapy offers a promising approach to cancer treatment by enabling patients to produce their own anti-angiogenic proteins, overcoming challenges associated with traditional therapies.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Tumor growth relies on angiogenesis, making its inhibition a key cancer treatment strategy.
- Clinical application of endogenous angiogenesis inhibitors is limited by high doses, manufacturing issues, and protein instability.
- Gene therapy presents an attractive alternative for delivering these therapeutic proteins.
Purpose of the Study:
- To evaluate the potential of anti-angiogenic gene therapy for cancer treatment.
- To review existing research on anti-angiogenic gene therapy models.
Main Methods:
- Systematic literature review using PubMed and cited references.
- Analysis of published anti-angiogenic gene therapy research.
Main Results:
- Over 40 endogenous angiogenesis inhibitors identified; 13 successfully used in gene therapy models with demonstrated antitumor effects.
- Inhibition of pro-angiogenic factors like vascular endothelial growth factor also explored.
- Systemic anti-angiogenic gene therapy shows success in preclinical models, utilizing host tissues for protein production.
Conclusions:
- Gene therapy allows cancer patients to produce their own anti-angiogenic proteins, circumventing clinical trial limitations of conventional agents.
- Anti-angiogenic gene therapy is a successful and evolving strategy in preclinical cancer models.
- This approach holds significant promise for future cancer therapeutics.