Rauth A M, Melo T, Misra V
Division of Experimental Therapeutics, Ontario Cancer Institute, Toronto, Canada.
Int J Radiat Oncol Biol Phys. 1998 Nov 1;42(4):755-62. doi: 10.1016/s0360-3016(98)00302-2.
Bioreductively activated drugs have been used as antimicrobials, chemotherapeutic agents, and radiation sensitizers. The present paper is an overview of their mechanism of action and application in the treatment of cancer.
Drugs such as nitroimidazoles, mitomycins, and benzotriazine di-N-oxides were a focus of this research. Studies have ranged from the chemistry of the reductive process of activation to in vitro and in vivo studies in rodent and human cells, through to clinical testing. The variety of techniques and test systems brought to bear on these compounds is a strength of this field of research.
A detailed chemical understanding of the mechanism of action of a variety of bioreductives is now available. The enzymatic processes by which these drugs are activated and the cofactors involved in this activation are becoming well understood. Recent advances have been made in the design and use of dual-function bioreductives, bioreductive triggers of drug activation, and DNA-targeted bioreductives. Significant success has been demonstrated clinically with bioreductive drugs, used in combination with radiation and front-line chemotherapeutic agents. The areas of antibody-directed enzyme prodrug therapy (ADEPT) and gene-directed enzyme prodrug therapy (GDEPT) are identified as new directions for bioreductive therapy.
The use of bioreductively-activated drugs for the treatment of cancer has made steady progress. The success obtained clinically and the new molecular approaches currently being implemented promise significant advances in the future.
生物还原激活药物已被用作抗菌剂、化疗药物和放射增敏剂。本文概述了它们的作用机制及其在癌症治疗中的应用。
硝基咪唑、丝裂霉素和苯并三嗪二氮氧化物等药物是本研究的重点。研究范围从激活的还原过程的化学，到在啮齿动物和人类细胞中的体外和体内研究，直至临床试验。应用于这些化合物的各种技术和测试系统是该研究领域的优势所在。
现在已经对多种生物还原剂的作用机制有了详细的化学认识。这些药物被激活的酶促过程以及参与这种激活的辅助因子正逐渐为人所熟知。在双功能生物还原剂、药物激活的生物还原触发剂和靶向DNA的生物还原剂的设计和使用方面取得了最新进展。生物还原药物与放射和一线化疗药物联合使用在临床上已取得显著成功。抗体导向酶前药疗法（ADEPT）和基因导向酶前药疗法（GDEPT）领域被确定为生物还原疗法的新方向。
使用生物还原激活药物治疗癌症已取得稳步进展。临床上取得的成功以及目前正在实施的新分子方法有望在未来取得重大进展。
