The role of estrogen and estrogen receptors in chemoresistance.
The role of estrogen and estrogen receptors in chemoresistance.
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DOI：
10.2174/092986711797379348
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发表时间：
2011-09
影响因子：
4.1
通讯作者：
M. Sui;H. Zhang;W. Fan
中科院分区：
文献类型：
--
作者：
M. Sui;H. Zhang;W. Fan
耐药性是限制癌症化疗成功的主要障碍之一。导致耐药性的生物学机制可能是从头出现的，与固有特征有关，也可能在暴露于抗癌药物后出现。近年来，临床观察和实验研究表明，类固醇激素及其受体也可能影响抗肿瘤药物的疗效。雌激素和雌激素受体（ER）在乳腺肿瘤的发生和发展中起着重要作用。长期以来，人们已经知道，表达ERα蛋白（ERα+）的乳腺肿瘤与ERα阴性（ERα-）肿瘤在对激素治疗的反应方面表现出根本不同的方式。从实验室和临床研究中获得的数据表明，一些化疗药物在ERα+肿瘤中的效果明显低于ERα-肿瘤，尽管ERα介导的化疗耐药机制尚不完全清楚。此外，我们实验室和其他实验室最近的研究表明，抗雌激素药物与化疗药物联合治疗ERα+乳腺癌比单独化疗具有显著的治疗益处。此外，ERα衍生肽、特异性靶向ERα的microRNA以及靶向雌激素相关受体（ERRs）的药物可能有望使ERα+乳腺肿瘤对化疗敏感。考虑到~ 65%的人类乳腺癌表达ER，ERα介导的化疗耐药性已成为临床治疗的一大挑战。克服这种耐药性的希望依赖于进一步阐明导致耐药性的特定途径或分子。因此，深入研究ERα阳性乳腺癌的化疗增敏机制，探索ERα阳性乳腺癌化疗增敏的新途径，具有重要意义。
Drug resistance is one of the major obstacles limiting the success of cancer chemotherapy. Biological mechanisms contributing to drug resistance may be present de novo and related to inherent features or may be raised after exposure to anticancer drugs. In recent years, both clinical observations and experimental studies suggested that steroid hormones and their receptors might also affect the therapeutic efficacy of antineoplastic drugs. Estrogens and estrogen receptors (ER) are well-known for their critical roles in the development and progression of breast tumors. It has long been known that breast tumors expressing ERα protein (ERα+) behave in a fundamentally different fashion than ERα-negative (ERα-) tumors with regard to their responses to hormonal therapy. Data obtained from both laboratory and clinical investigations suggested that some chemotherapeutic agents are clearly less effective in ERα+ tumors than ERα- tumors, although the mechanisms of ERα-mediated chemoresistance are not entirely clear. Moreover, recent studies from our laboratory and others demonstrated that the combination of antiestrogenic agents with chemotherapeutic drugs is of significant therapeutic benefit in ERα+ breast cancer over chemotherapy alone. In addition, the ERα-derived peptides, microRNAs specifically targeting ERα, as well as agents targeting estrogen-related receptors (ERRs) may hold promise to sensitize ERα+ breast tumors to chemotherapy. Considering that ERs are expressed in ˜ 65% of human breast cancer, the ERα-mediated chemoresistance has become a big challenge for clinical treatment. The hope to overcome this drug resistance relies on further clarification of specific pathways or molecules contributing to the resistance. More exhaustive and systematic studies are essential to reach deeper understandings on the underlying mechanisms and to develop novel approaches to sensitize ERα+ breast tumors to chemotherapy.