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Radiation-guided gene therapy of cancer
Zhaozhong Han1, Hailun Wang, Dennis E Hallahan
1Department of Radiation Oncology, School of Medicine, Vanderbilt University, 1161 21st Ave. South, Nashville, TN 37232, USA.
Abstract:
Gene therapy has been proposed as a means to combat cancer. However, systemic toxicity observed in preclinical trials suggested the importance of selectively targeted delivery and inducible gene expression in tumor tissues. Discovery of radiation-inducible promoter sequences provides one way to minimize inadvertent toxicity from gene therapy in normal tissues. Radiation is administered to selectively induce cytotoxic gene expression in the targeted tumor tissues. With promising results from phase II clinical trials using TNF-expressing adenovirus, it is possible to have radiation-guided gene therapy regimes once the tumor-targeted delivery has been achieved. Tumor endothelium is an attractive biological target for gene therapy, because it has the advantage of stability, accessibility, and bioavailability for therapeutic agents. Technological development of DNA microarray, proteomic profiling, and phage-displayed libraries accelerates the identification of tumor-specific endothelial biomarkers and discovery of its relevant affinity reagents for targeted delivery. The application of radiation-guided gene delivery, its amplification, as well as expression of gene therapy presents great opportunities to be employed as an alternative cancer treatment.
Insights
Radiation-guided gene therapy offers a promising cancer treatment by selectively targeting tumors and minimizing toxicity. This approach uses radiation to activate gene expression specifically within cancer cells, enhancing therapeutic efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Systemic toxicity in early gene therapy trials necessitates targeted delivery and inducible expression.
- Radiation-inducible promoters offer a strategy to confine gene therapy effects to tumor tissues.
- Tumor endothelium presents a viable target for gene therapy due to its accessibility and stability.
Purpose of the Study:
- To explore radiation-guided gene therapy as a method for cancer treatment.
- To investigate the potential of targeting tumor endothelium for enhanced gene delivery.
- To leverage technological advancements for identifying tumor-specific biomarkers and affinity reagents.
Main Methods:
- Utilizing radiation-inducible promoter sequences for controlled gene expression.
- Developing tumor-targeted delivery systems, potentially focusing on tumor endothelium.
- Employing technologies like DNA microarrays and proteomic profiling for biomarker discovery.
Main Results:
- Phase II clinical trials show promise for adenovirus-mediated tumor necrosis factor (TNF) gene therapy.
- Identification of tumor-specific endothelial biomarkers and affinity reagents is accelerated by advanced technologies.
- Radiation-guided gene delivery, amplification, and expression demonstrate potential in preclinical settings.
Conclusions:
- Radiation-guided gene therapy represents a novel and potentially safer alternative for cancer treatment.
- Targeting tumor endothelium combined with radiation-inducible gene expression enhances therapeutic specificity.
- Technological advancements are crucial for the successful development and application of this gene therapy approach.
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