Hanstein B, Djahansouzi S, Dall P, Beckmann M W, Bender H G
Universitats-Frauenklinik, Heinrich Heine Universitat, Moorenstrasse 5, D-40225 Dusseldorf, Germany.
Eur J Endocrinol. 2004 Mar;150(3):243-55. doi: 10.1530/eje.0.1500243.
Evidence for a role of ovarian factors in the growth of metastatic breast cancer was first recognized over 100 years ago. Today, anti-estrogens are central to the treatment of breast cancer of all stages. We now understand that the action of estrogen is mediated by the estrogen receptors (ER) which are members of the nuclear receptor family of ligand-regulated transcription factors. In this article we review the molecular mechanisms through which ER activates transcription of target genes and through which available anti-estrogens mediate their therapeutic effects. We discuss possible mechanisms of failure of treatment with current anti-estrogens and how newer anti-estrogens under development attempt to address these problems. In addition an expanded view of the molecular mechanisms of estrogen action is leading to the development of novel selective ER modulators or SERMs.
卵巢因素在转移性乳腺癌生长中所起作用的证据早在100多年前就首次得到确认。如今,抗雌激素药物是各期乳腺癌治疗的核心。我们现在明白,雌激素的作用是由雌激素受体(ER)介导的,雌激素受体是配体调节转录因子核受体家族的成员。在本文中,我们综述了雌激素受体激活靶基因转录以及现有抗雌激素药物发挥治疗作用的分子机制。我们讨论了当前抗雌激素药物治疗失败的可能机制,以及正在研发的新型抗雌激素药物如何试图解决这些问题。此外,对雌激素作用分子机制的进一步认识正促使新型选择性雌激素受体调节剂(SERM)的开发。