Schepelmann Silke, Springer Caroline J
The Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, 15 Cotswold Road, Sutton SM2 5NG, Surrey, UK.
Curr Gene Ther. 2006 Dec;6(6):647-70. doi: 10.2174/156652306779010679.
Conventional cancer treatments are often hampered by a lack of tumour selectivity, resulting in toxicity to healthy tissue. Gene-directed enzyme prodrug therapy (GDEPT) is a suicide gene therapy approach that aims to improve the selectivity of chemotherapy by enabling cancer cells to convert non-cytotoxic prodrugs to cytotoxic drugs. Many enzyme/prodrug systems have been described, some of which have already been tested in clinical trials. A key component of GDEPT is a foreign enzyme that is expressed selectively at the tumour site where it converts the prodrug into the cytotoxic agent. The gene encoding the prodrug-activating enzyme needs to be expressed selectively and efficiently in tumour cells in order to spare normal tissue from damage. Substantial efforts have been made to develop gene therapy vectors that are capable of targeting cancer cells. A large number of gene delivery systems have been described for GDEPT: Viral vectors are the most advanced. They include replication-deficient and replication-selective (oncolytic) viruses. Recent advances in engineering viruses for GDEPT are reviewed in this article and data from both preclinical studies and clinical trials are discussed.
传统的癌症治疗方法常常因缺乏肿瘤选择性而受到阻碍，导致对健康组织产生毒性。基因导向酶前药疗法（GDEPT）是一种自杀基因疗法，旨在通过使癌细胞将无细胞毒性的前药转化为细胞毒性药物来提高化疗的选择性。已经描述了许多酶/前药系统，其中一些已经在临床试验中进行了测试。GDEPT的一个关键组成部分是一种外源酶，它在肿瘤部位选择性表达，在那里它将前药转化为细胞毒性剂。为了使正常组织免受损伤，编码前药激活酶的基因需要在肿瘤细胞中选择性且高效地表达。人们已经付出了巨大努力来开发能够靶向癌细胞的基因治疗载体。已经为GDEPT描述了大量的基因递送系统：病毒载体是最先进的。它们包括复制缺陷型和复制选择性（溶瘤）病毒。本文综述了用于GDEPT的病毒工程的最新进展，并讨论了临床前研究和临床试验的数据。
