环磷酰胺的药物基因组学研究进展

Advances in the research of pharmacogenomics of cyclophosphamide

环磷酰胺(cyclophosphamide,CPA)作为最常用的烷化剂类抗肿瘤药物,也常用于自身免疫性疾病及器官移植后的治疗。CPA主要通过肝脏的细胞色素P450酶代谢为活性产物,从而发挥药理作用。该药具有严重的毒副作用,且疗效和不良反应具有显著的个体差异。本文总结了CPA体内过程相关的代谢酶及转运体等的基因多态性与CPA疗效/毒性的相关性,为进一步的药物基因组学研究提供参考。

Cyclophosphamide（CPA） is the most common alkylating antineoplastic agent, as well as a strong immunosuppressant that is frequently applied to autoimmune diseases and organ transplantation. It is metabolized by cytochrome P450 oxidases（CYPs） to its active metabolite which played a critical role in therapy. CPA has serious and even fatal side effects, and its efficacy and adverse reactions are significantly varied among individuals. In this review, the association of the genetic polymorphisms in the metabolic enzymes and transporters involved in the disposition of CPA with the efficacy and adverse effects of CPA were summarized, thereby providing fundamental reference for further pharmacogenomic study of CPA.