Current progress in suicide gene therapy for cancer.
Standard chemotherapeutic agents and ionizing radiation destroy dividing cells. Because tumor cells divide more rapidly than normal cells, there is a therapeutic index in which damage to the cancer cells is maximized while keeping the toxicity to the normal host cells acceptable. Suicide gene therapy strives to deliver genes to the cancer cells, which convert nontoxic prodrugs into active chemotherapeutic agents. With this strategy, the systemically administered prodrug is converted to the active chemotherapeutic agent only in cancer cells, thereby allowing a maximal therapeutic effect while limiting systemic toxicity. A literature search was conducted using the MEDLINE database from 1990 to 2001 to identify articles related to suicide gene therapy for cancer. A number of suicide gene systems have been identified, including the herpes simplex virus thymidine kinase gene, the cytosine deaminase gene, the varicella-zoster virus thymidine kinase gene, the nitroreductase gene, the Escherichia coli gpt gene, and the E. coli Deo gene. Various vectors, including liposomes, retroviruses, and adenoviruses, have been used to transfer these suicide genes to tumor cells. These strategies have been effective in cell culture experiments, laboratory animals, and some early clinical trials. Advances in tissue- and cell-specific delivery of suicide genes using specific promoters will improve the clinical utility of suicide gene therapy.
Yazawa
Kazuyuki
K
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 6550 Fannin, Suite 1661, Houston, Texas 77030, USA.
Fisher
William E
WE
Brunicardi
F Charles
FC
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001087:Arabinonucleosides / Q000494:pharmacology; D001388:Aziridines / Q000494:pharmacology; D002986:Clinical Trials as Topic; D043525:Cytosine Deaminase; D004926:Escherichia coli / Q000235:genetics; D005437:Flucytosine / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000494:pharmacology; D014645:Herpesvirus 3, Human / Q000201:enzymology; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D009601:Nitroreductases / Q000235:genetics / Q000378:metabolism; D009700:Nucleoside Deaminases / Q000378:metabolism; D010430:Pentosyltransferases / Q000235:genetics / Q000378:metabolism; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*; D011684:Purine Nucleosides / Q000494:pharmacology; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology
D000998:Antiviral Agents; D001087:Arabinonucleosides; D001388:Aziridines; D011355:Prodrugs; D011684:Purine Nucleosides; D014970:Xanthines; C032885:6-methylpurine 2'-deoxyriboside; C054700:6-thioxanthine; C100099:tretazicar; C069956:6-methoxypurine arabinoside; D005437:Flucytosine; D009601:Nitroreductases; D010430:Pentosyltransferases; D013937:Thymidine Kinase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase; D015774:Ganciclovir