Portsmouth Daniel, Hlavaty Juraj, Renner Matthias
Research Institute for Virology and Biomedicine, University of Veterinary Medicine, Vienna, Austria.
Mol Aspects Med. 2007 Feb;28(1):4-41. doi: 10.1016/j.mam.2006.12.001. Epub 2007 Jan 10.
The principle of using suicide genes for gene directed enzyme prodrug therapy (GDEPT) of cancer has gained increasing significance during the 20 years since its inception. The astute application of suitable GDEPT systems should permit tumour ablation in the absence of off-target toxicity commonly associated with classical chemotherapy, a hypothesis which is supported by encouraging results in a multitude of pre-clinical animal models. This review provides a clear explanation of the rationale behind the GDEPT principle, outlining the advantages and limitations of different GDEPT strategies with respect to the roles of the bystander effect, the immune system and the selectivity of the activated prodrug in contributing to their therapeutic efficacy. An in-depth analysis of the most widely used suicide gene/prodrug combinations is presented, including details of the latest advances in enzyme and prodrug optimisation and results from the most recent clinical trials.
自癌症基因导向酶前体药物疗法（GDEPT）中使用自杀基因的原理问世20年来，其重要性日益凸显。合理应用合适的GDEPT系统应能在不存在与传统化疗常见的脱靶毒性的情况下实现肿瘤消融，这一假设在众多临床前动物模型中取得的鼓舞人心的结果得到了支持。本综述清晰解释了GDEPT原理背后的基本原理，概述了不同GDEPT策略在旁观者效应、免疫系统以及活化前体药物的选择性对其治疗效果的贡献方面的优缺点。对最广泛使用的自杀基因/前体药物组合进行了深入分析，包括酶和前体药物优化的最新进展细节以及最新临床试验结果。
