Eliason James F, Megyeri Attila
Barbara Ann Karmanos Cancer Institute, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48230, USA.
Curr Drug Targets. 2004 May;5(4):383-8. doi: 10.2174/1389450043345461.
The efficacy of cancer therapy is compromised by the fact that there are currently no good ways to predict which patients will benefit from treatment. This long standing goal is closer to becoming a reality as more is learned about the molecules that affect the activities of various therapeutic agents. The fluoropyrimidine antimetabolites drugs have been in clinical use for over 4 decades and the cellular proteins important for their activities have been studied in detail. The most important are the major target enzyme, thymidylate synthase (TS) and the rate limiting enzyme in the degradation pathway, dihydropyrimidine dehydrogenase (DPD), equally important for the analogue capecitabine is thymidine phosphorylase (TP), which is rate limiting for activation of this prodrug. A number of assays are available for these enzymes, including enzyme activity measurements. quantitative PCR for RNA expression and immunological methods for protein expression. With each of these methods, more clinical studies are required to validate their clinical usefulness.
癌症治疗的疗效受到目前缺乏有效方法来预测哪些患者将从治疗中获益这一事实的影响。随着我们对影响各种治疗药物活性的分子有了更多了解，这一长期目标正越来越接近现实。氟嘧啶抗代谢药物已在临床使用超过40年，对其活性起重要作用的细胞蛋白已得到详细研究。其中最重要的是主要靶酶胸苷酸合成酶（TS）以及降解途径中的限速酶二氢嘧啶脱氢酶（DPD），对于类似物卡培他滨同样重要的是胸苷磷酸化酶（TP），它是该前体药物激活的限速酶。有多种针对这些酶的检测方法，包括酶活性测定、RNA表达定量PCR以及蛋白质表达免疫方法。对于每种方法，都需要更多的临床研究来验证其临床实用性。
