Mechanisms of resistance to aromatase inhibitors
Mechanisms of resistance to aromatase inhibitors
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DOI：
10.1016/j.jsbmb.2005.04.022
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发表时间：
2005-05-01
影响因子：
4.1
通讯作者：
Johnston, S
中科院分区：
文献类型：
--
作者：
Dowsett, M;Martin, LA;Johnston, S
芳香化酶抑制剂正迅速成为绝经后妇女类固醇受体阳性乳腺癌激素治疗的首选。因此，了解这些药物的耐药机制对于向有反应的患者提供适当的治疗以及合理开发针对耐药途径的新药非常重要。从头耐药似乎是一种定量而非定性现象，几乎所有雌激素受体阳性肿瘤均对芳香化酶抑制剂阿那曲唑表现出抗增殖反应。虽然I型生长因子受体的表达降低了对他莫昔芬的反应，但这似乎对对芳香酶抑制剂的反应几乎没有不利影响。体外获得性耐药研究表明，获得对雌激素刺激的超敏反应是一个关键机制，依赖于生长因子和雌激素信号通路的增强串扰。从患者中收集耐药活检组织对于确定该机制是否具有临床相关性非常重要。(c)2005爱思唯尔有限公司保留所有权利。
Aromatase inhibitors are rapidly becoming the first choice for hormonal treatment of steroid receptor positive breast cancer in postmenopausal women. An understanding of the resistance mechanisms to these agents is, therefore, important for the appropriate delivery of treatment to responsive patients and the rational development of new agents targeted at the resistance pathways. De novo resistance appears to be a quantitative rather than qualitative phenomenon with virtually all oestrogen receptor positive tumours showing an anti-proliferative response to the aromatase inhibitor anastrozole. While the expression of type I growth factor receptors reduces response to tamoxifien this appears to have little detrimental effect on response to aromatase inhibitors. Studies of acquired resistance in vitro have indicated that acquisition of hypersensitivity to oestrogenic stimulation is a key mechanism that is dependent on enhanced cross-talk of growth factor and oestrogen signaling pathways. Collection of resistant biopsy tissues from patients is important to determine if this mechanism is clinically relevant. (c) 2005 Elsevier Ltd. All rights reserved.