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乳腺癌的药物遗传学:重点关注激素治疗、紫杉烷类药物、曲妥珠单抗和贝伐珠单抗。

Pharmacogenetics in breast cancer: focus on hormone therapy, taxanes, trastuzumab and bevacizumab.

机构信息

San Filippo Neri Hospital, Rome, Italy.

出版信息

Expert Opin Investig Drugs. 2010 Apr;19 Suppl 1:S41-50. doi: 10.1517/13543781003732701.

Abstract

Breast cancer is the most common female cancer, with more than one million new patients diagnosed annually worldwide. The great heterogeneity, in terms of prognosis and outcome, within patients with the same clinical and pathological characteristics may limit the potential for personalized therapy. Most of the cytotoxic agents and new targeted agents have a narrow therapeutic index and the administration of an equal dose may result in a wide range of toxicities as well as to different antitumor efficacy. Inter-subject variability in drug toxicity and response is common during treatment, so that individualization of treatments is an important issue. Pharmacogenetics is the study of how inter-individual variations in the DNA sequence of specific genes may affect drug response and toxicity. This article highlights the clinical use of determination of polymorphisms of important human drug-metabolizing cytochrome P450s, ABCB1, IgG fragment C receptors and vascular endothelial growth factor, which are responsible of the large inter-individual variability in drug metabolism and clearance of the agents commonly used in breast cancer treatment, such as tamoxifen, aromatase inhibitors, taxanes, trastuzumab and bevacizumab.

摘要

乳腺癌是最常见的女性癌症,全球每年有超过 100 万新患者被诊断。在具有相同临床和病理特征的患者中,预后和结果存在很大的异质性,这可能限制了个性化治疗的潜力。大多数细胞毒性药物和新型靶向药物的治疗指数较窄,给予相同剂量可能会导致广泛的毒性和不同的抗肿瘤疗效。在治疗过程中,药物毒性和反应的个体间变异性很常见,因此治疗的个体化是一个重要问题。药物遗传学是研究特定基因的 DNA 序列个体间差异如何影响药物反应和毒性的学科。本文重点介绍了确定重要的人类药物代谢细胞色素 P450s、ABCB1、IgG 片段 C 受体和血管内皮生长因子多态性的临床应用,这些多态性决定了乳腺癌治疗中常用药物(如他莫昔芬、芳香酶抑制剂、紫杉烷类、曲妥珠单抗和贝伐珠单抗)的药物代谢和清除的个体间变异性很大。

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