Department of Biochemistry and Microbial Sciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab, 151001, India.
Cancer Chemother Pharmacol. 2019 Dec;84(6):1157-1166. doi: 10.1007/s00280-019-03936-w. Epub 2019 Sep 4.
Cancer caused by fundamental defects in cell cycle regulation leads to uncontrolled growth of cells. In spite of the treatment with chemotherapeutic agents of varying nature, multiple resistance mechanisms are identified in cancer cells. Similarly, numerous variations, which decrease the metabolism of chemotherapeutics agents and thereby increasing the toxicity of anticancer drugs have been identified. 5-Fluorouracil (5-FU) is an anticancer drug widely used to treat many cancers in the human body. Its broad targeting range is based upon its capacity to act as a uracil analogue, thereby disrupting RNA and DNA synthesis. Dihydropyrimidine dehydrogenase (DPD) is an enzyme majorly involved in the metabolism of pyrimidines in the human body and has the same metabolising effect on 5-FU, a pyrimidine analogue. Multiple mutations in the DPD gene have been linked to 5-FU toxicity and inadequate dosages. DPD inhibitors have also been used to inhibit excessive degradation of 5-FU for meeting appropriate dosage requirements. This article focusses on the role of dihydropyrimidine dehydrogenase in the metabolism of the anticancer drug 5-FU and other associated drugs.
癌症是由于细胞周期调控的根本缺陷引起的，导致细胞不受控制地生长。尽管使用了性质各异的化疗药物进行治疗，但在癌细胞中已经确定了多种耐药机制。同样，也发现了许多变异，这些变异会降低化疗药物的代谢速度，从而增加抗癌药物的毒性。5-氟尿嘧啶（5-FU）是一种广泛用于治疗人体多种癌症的抗癌药物。它的广泛靶向范围基于其作为尿嘧啶类似物的作用能力，从而破坏 RNA 和 DNA 的合成。二氢嘧啶脱氢酶（DPD）是一种主要参与嘧啶代谢的酶，对嘧啶类似物 5-FU 也有相同的代谢作用。DPD 基因的多种突变与 5-FU 毒性和剂量不足有关。还使用 DPD 抑制剂来抑制 5-FU 的过度降解，以满足适当的剂量要求。本文重点介绍二氢嘧啶脱氢酶在抗癌药物 5-FU 及其他相关药物代谢中的作用。
