二氢嘧啶脱氢酶和胸腺嘧啶核苷激酶的研究进展

Advance in dihydropyrimidine dehydrogenase and thymidine kinase influencing on the clinical therapy of pyrimidine chemotherapy drugs

目的:了解二氢嘧啶脱氢酶（DPD）和胸腺嘧啶核苷激酶（TK）的研究现状和在临床肿瘤治疗中的意义。方法:综述近年来DPD和TK的研究现状及其在临床肿瘤治疗中的应用。结果:DPD存在的个体差异导致氟尿嘧啶治疗中肿瘤细胞对药物的敏感性的不同,从而导致疗效的不同;TK的活性高低一定程度上反映了细胞中DNA的合成速度,可以用于临床诊断肿瘤细胞增殖程度和解释应用嘧啶类化疗药物时的疗效和毒性反应。结论:认识和利用这两种酶的作用机制以及个体差异不仅可以指导临床的个体化治疗,减小药物的不良反应和增加疗效,而且可以辅助肿瘤的诊断和指导嘧啶类新药的开发。

OBJECTIVE: To provide the advances of the research in dihydropyrimidine dehydrogenase (DPD) and thymidine kinase (TK) and the significances of their applications in clinical tumor chemotherapy. METHOD: Advances in research and application in clinical tumor chemotherapy of two pyrimidine metabolic enzymes were reviewed. RESULT: Discrepancy of DPD among individuals is the key factor to determine the difference in the tumor sensitivity to pyrimidine drug and, in turn, cause the difference in curative effects. The activity of TK, to some extent, reflects the DNA synthesis rate in cells, which can be used to detect the rates of tumor cells proliferation and explain the curative effects and side effects during pyrimidines administration. CONCLUSION: Understanding and utilizing the function mechanisms and individual differences of these two enzymes not only guides clinical individual pyrimidines chemotherapy, decreasing side effects and increasing curative effects, but also gives some aids on tumor diagnosis and directs the development of novel pyrimidine drugs.