Use of hypoxia-regulated gene expression in tumor-specific gene therapy.
The presence of hypoxic cells in human solid tumors is an important factor leading to resistance to radiation therapy and chemotherapy. However, differences in the oxygen tension between normal tissues and tumors also provide the potential for designing tumor-specific gene therapy. The strategy is to selectively induce the expression of suicide genes under hypoxia and thereby preferentially kill hypoxic cells. The hypoxia-responsive vector regulates gene expression via the hypoxia-responsive element, which can be activated through the transcriptional complex hypoxia-inducible factor 1. A gene therapy that is based on hypoxia-regulated gene expression needs to consider the suicide gene, the genetic vector, the delivery method and the bystander effect. These factors pose considerable challenges for the development of a successful hypoxia-directed gene therapy, but once this has been achieved, this type of therapy in combination with traditional radiation and chemotherapy should provide an improved clinical outcome for patients with these diseases.
Ruan
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Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco 94143-0520, USA.
Deen
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DF
D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D000860:Hypoxia / Q000235:genetics*; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D015398:Signal Transduction / Q000235:genetics