Dachs Gabi U, Tupper Joanna, Tozer Gillian M
Angiogenesis Research Group, Department of Pathology, Christchurch School of Medicine and Health Sciences, University of Otago, Christchurch, New Zealand.
Anticancer Drugs. 2005 Apr;16(4):349-59. doi: 10.1097/00001813-200504000-00001.
Gene therapy of cancer offers the possibility of a targeted treatment that destroys tumors and metastases, but not normal tissues. In gene-directed enzyme prodrug therapy (GDEPT), or suicide gene therapy, the gene encoding an enzyme is delivered to tumor cells, followed by administration of a prodrug, which is converted locally to a cytotoxin by the enzyme. The producer cells as well as surrounding bystanders are subsequently killed. Promising results have meant that suicide gene therapy has reached multicenter phase III clinical trials. This review will discuss the development, efficiency, mode of action and pharmacokinetics of seven GDEPT systems in vitro and in vivo. We will review the latest data of those systems in clinical trials (herpes simplex virus thymidine kinase/gancyclovir, bacterial cytosine deaminase/5-fluorocytosine, bacterial nitroreductase/CB1954 and cytochrome P450/cyclophosphamide), as well as the development of more recent and experimental systems which are not yet in clinical trials (P450 reductase/tirapazamine, carboxypeptidase/CMDA, horseradish peroxidase/indole-3-acetic acid or paracetamol and others).
癌症的基因治疗提供了一种靶向治疗的可能性，即破坏肿瘤和转移灶，而不损伤正常组织。在基因导向酶前体药物疗法（GDEPT）或自杀基因疗法中，编码一种酶的基因被导入肿瘤细胞，随后给予一种前体药物，该前体药物被酶在局部转化为细胞毒素。随后，产生酶的细胞以及周围的旁观者细胞都会被杀死。有前景的结果意味着自杀基因疗法已进入多中心III期临床试验。本综述将讨论七种GDEPT系统在体外和体内的发展、效率、作用方式和药代动力学。我们将回顾这些系统在临床试验中的最新数据（单纯疱疹病毒胸苷激酶/更昔洛韦、细菌胞嘧啶脱氨酶/5-氟胞嘧啶、细菌硝基还原酶/CB1954和细胞色素P450/环磷酰胺），以及尚未进入临床试验的更新的实验系统（P450还原酶/替拉扎明、羧肽酶/CMDA、辣根过氧化物酶/吲哚-3-乙酸或对乙酰氨基酚等）的发展情况。
