Department of Biochemistry, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151001, India.
Clin Transl Oncol. 2020 Oct;22(10):1667-1680. doi: 10.1007/s12094-020-02325-7. Epub 2020 Mar 13.
Although continuous researches are going on for the discovery of new chemotherapeutic agents, resistance to these anticancer agents has made it really difficult to reach the fruitful results. There are many causes for this resistance that are being studied by the researchers across the world, but still, success is far because there are several factors that are going along unattended or have been studied less. Drug-metabolizing enzymes (DMEs) are one of these factors, on which less study has been conducted. DMEs include Phase I and Phase II enzymes. Cytochrome P450s (CYPs) are major Phase I enzymes while glutathione-S-transferases (GSTs), UDP-glucuronosyltransferases (UGTs), dihydropyrimidine dehydrogenases are the major enzymes belonging to the Phase II enzymes. These enzymes play an important role in detoxification of the xenobiotics as well as the metabolism of drugs, depending upon the tissue in which they are expressed. When present in tumorous tissues, they cause resistance by metabolizing the drugs and rendering them inactive. In this review, the role of these various enzymes in anticancer drug metabolism and the possibilities for overcoming the resistance have been discussed.
虽然不断进行研究以发现新的化疗药物，但这些抗癌药物的耐药性使得很难取得丰硕的成果。这种耐药性有很多原因，全世界的研究人员都在研究，但仍然远远没有成功，因为有几个因素没有得到关注或研究较少。药物代谢酶（DMEs）就是其中一个因素，对其研究较少。DMEs 包括 I 相和 II 相酶。细胞色素 P450s（CYPs）是主要的 I 相酶，而谷胱甘肽-S-转移酶（GSTs）、UDP-葡萄糖醛酸转移酶（UGTs）、二氢嘧啶脱氢酶则是属于 II 相酶的主要酶。这些酶根据其表达的组织在解毒外来物质和药物代谢中发挥重要作用。当存在于肿瘤组织中时，它们通过代谢药物使其失活而产生耐药性。在这篇综述中，讨论了这些各种酶在抗癌药物代谢中的作用以及克服耐药性的可能性。
