ABC转运蛋白的药物基因组学及其在癌症化疗中的作用。

Pharmacogenomics of ABC transporters and its role in cancer chemotherapy.

作者信息

Sparreboom Alex, Danesi Romano, Ando Yuichi, Chan Juliana, Figg William D

机构信息

Clinical Pharmacology Research Core, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

出版信息

Drug Resist Updat. 2003 Apr;6(2):71-84. doi: 10.1016/s1368-7646(03)00005-0.

DOI:10.1016/s1368-7646(03)00005-0

PMID:12729805

Abstract

ATP-binding cassette (ABC) genes play a role in the resistance of malignant cells to anticancer agents. The ABC gene products, including ABCB1 (P-glycoprotein), ABCC1 (MRP1), ABCC2 (MRP2, cMOAT), and ABCG2 (BCRP, MXR, ABCP) are also known to influence oral absorption and disposition of a wide variety of drugs. As a result, the expression levels of these proteins in humans have important consequences for an individual's susceptibility to certain drug-induced side effects, interactions, and treatment efficacy. Naturally occurring variants in ABC transporter genes have been identified that might affect the function and expression of the protein. This review focuses on recent advances in the pharmacogenomics of ABC transporters, and discusses potential implications of genetic variants for the chemotherapeutic treatment of cancer.

摘要

ATP结合盒（ABC）基因在恶性细胞对抗癌药物的耐药性中起作用。ABC基因产物，包括ABCB1（P-糖蛋白）、ABCC1（多药耐药相关蛋白1，MRP1）、ABCC2（多药耐药相关蛋白2，MRP2，胆小管多特异性有机阴离子转运体，cMOAT）和ABCG2（乳腺癌耐药蛋白，BCRP，多药耐药蛋白，MXR，ABCP）也已知会影响多种药物的口服吸收和处置。因此，这些蛋白质在人体内的表达水平对个体对某些药物诱导的副作用、相互作用和治疗效果的易感性具有重要影响。已鉴定出ABC转运蛋白基因中的天然变异体，这些变异体可能会影响蛋白质的功能和表达。本综述重点关注ABC转运蛋白药物基因组学的最新进展，并讨论基因变异对癌症化疗治疗的潜在影响。