【作者】 张燕青； 王连生；

【Author】 ZHANG Yan-qing,WANG Lian-sheng (Institute of Clinical Pharmacology,Central South University,Changsha 410078,China)

【机构】 中南大学临床药理研究所；

【摘要】 他莫昔芬是治疗乳腺癌抗雌激素金标准药物,但临床上雌激素受体α阳性的乳腺癌患者中有30%～50%对其耐药。他莫昔芬耐药机制部分与基因变异有关。代谢酶细胞色素氧化酶P450 CYP2D6,细胞色素P450 CYP2C19,细胞色素P450 CYP3A5以及磺基转移酶1A1基因多态在一些特定人群中与他莫昔芬疗效显著相关,转运体ABCC2以及雌激素受体基因型对他莫昔芬疗效也具有显著影响。他莫昔芬相关的遗传药理学研究正在不断深入揭示该药耐药的遗传学基础,尽管有些发现尚需进一步阐述,但一些成果已经开始发挥临床药物治疗的指导作用。更多还原

【Abstract】 Tamoxifen has been the gold standard for endocrine treatment of breast cancer patients of estrogen receptor(ER)-positive.However,30%-50%of the patients have been found to display tamoxifen resistance. Genetic polymorphisms of metabolizing enzymes CYP2D6,CYP2C19,and SULT1A1 were found significantly associated with anticancer effects of tamoxifen.ABC transporter gene ABCC2 and estrogen receptor gene polymorphisms were also found to play considerable roles in tamoxifen’s response.Although the impact of some gene polymorphisms on the effect of tamoxifen still need to be clarified,all the pharmacogenetic informations about tamoxifen will finally be put together to provide the whole profile of the genetic basis for tamoxifen’s drug resistance.Achievements in this area such as the finding of the stable relation of CYP2D6 genotypes and tamoxifen response,will help to find practical ways to improve tamoxifen therapy.更多还原