Estrogen signaling pathway and hormonal therapy
Estrogen signaling pathway and hormonal therapy
复制标题
DOI：
10.1007/s12282-008-0070-z
复制
发表时间：
2008-10-01
期刊：
影响因子：
4
通讯作者：
Yamaguchi, Yuri
中科院分区：
文献类型：
--
作者：
Hayashi, Shin-ichi;Yamaguchi, Yuri
激素治疗，如雌激素靶向治疗，近年来经历了显着的发展，使用的药物，如LH-RH激动剂，新的SERM和第三代芳香酶抑制剂。几项正在进行的大规模激素治疗国际临床试验正在建立这些药物治疗的标准方案。另一方面，已经尝试使用经典的分子生物标志物如ER和PgR来预测激素治疗的个体功效。然而，大约三分之一的ER α阳性患者对内分泌治疗无反应，而一些ER α阴性患者有反应。这些差异可能是由于乳腺癌细胞中不同的雌激素相关的细胞内信号通路。此外，激素治疗在某些个体中无效（例如，由于芳香酶抑制剂耐药性）可能是由这些机制引起的。在本文中，我们讨论了这些不同的反应激素治疗的分子机制和乳腺癌细胞中的雌激素信号通路的影响。此外，我们还涉及到预测激素治疗疗效的基础研究和这一领域的新策略。
Hormonal therapy, such as estrogen-targeting therapy, has undergone remarkable development in recent several years, using drugs such as LH-RH agonists, new SERMs and third-generation aromatase inhibitors. Several ongoing large-scale international clinical trials for hormonal therapy are establishing the standard protocol for treatments with these drugs. On the other hand, there have been attempts to predict the individual efficacy of hormonal therapy using classical molecular biomarkers such as ER and PgR. However, approximately one-third of ER alpha-positive patients do not respond to endocrine therapy, while some ER alpha-negative patients are responsive. These discrepancies may be due to the different estrogen-related intracellular signaling pathways in breast cancer cells. Furthermore, the ineffectiveness of hormonal therapy in some individuals (due to, for example, aromatase inhibitor resistance) may be caused by these mechanisms. In this paper, we discuss the molecular mechanisms of these different responses to hormonal therapies and their implications for the estrogen signaling pathway in breast cancer cells. Furthermore, we touch upon basic studies into predicting the efficacy of hormonal therapy and new strategies in this field.