尿苷二磷酸葡萄糖醛酸转移酶药物遗传学在癌症治疗和预防中的潜在作用：聚焦于他莫昔芬
Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen.
作者信息
Lazarus Philip, Blevins-Primeau Andrea S, Zheng Yan, Sun Dongxiao
机构信息
Cancer Control and Population Sciences Program, Penn State Cancer Institute, Department of Pharmacology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA.
出版信息
Ann N Y Acad Sci. 2009 Feb;1155:99-111. doi: 10.1111/j.1749-6632.2009.04114.x.
Abstract
Tamoxifen (TAM) is a selective estrogen receptor modulator that is widely used in the prevention and treatment of estrogen receptor-positive (ER(+)) breast cancer. Its use has significantly contributed to a decline in breast cancer mortality, since breast cancer patients treated with TAM for 5 years exhibit a 30-50% reduction in both the rate of disease recurrence after 10 years of patient follow-up and occurrence of contralateral breast cancer. However, in patients treated with TAM there is substantial interindividual variability in the development of resistance to TAM therapy, and in the incidence of TAM-induced adverse events, including deep vein thrombosis, hot flashes, and the development of endometrial cancer. This article will focus on the UDP glucuronosyltransferases, a family of metabolizing enzymes that are responsible for the deactivation and clearance of TAM and TAM metabolites, and how interindividual differences in these enzymes may play a role in patient response to TAM.
摘要
他莫昔芬（TAM）是一种选择性雌激素受体调节剂，广泛用于预防和治疗雌激素受体阳性（ER(+)）乳腺癌。它的使用显著降低了乳腺癌死亡率，因为接受TAM治疗5年的乳腺癌患者在10年的患者随访后疾病复发率和对侧乳腺癌发生率均降低了30%-50%。然而，在接受TAM治疗的患者中，对TAM治疗产生耐药性以及发生TAM诱导的不良事件（包括深静脉血栓形成、潮热和子宫内膜癌）的个体间存在很大差异。本文将重点关注UDP葡萄糖醛酸转移酶，这是一类代谢酶，负责TAM及其代谢产物的失活和清除，以及这些酶的个体差异如何在患者对TAM的反应中发挥作用。
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