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微小 RNA 与乳腺癌耐药:基础证据与临床应用。

MicroRNAs and drug resistance of breast cancer: basic evidence and clinical applications.

机构信息

Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.

出版信息

Clin Transl Oncol. 2013 May;15(5):335-42. doi: 10.1007/s12094-012-0929-5. Epub 2012 Aug 23.

Abstract

Breast cancer is the most common malignancy and leading cause of cancer mortality in women. Drug resistance is a major obstacle in systemic therapy of breast cancer, which leads therapeutic failure, incontrollable disease, and mortality. MiRNAs are an emerging field in cancer research. Recent evidence demonstrates that miRNAs are core regulators in drug resistance of breast cancer. Preclinical research reveals that miRNAs modulate the multidrug-resistant signal transduction network through up-regulated drug efflux transporters and anti-apoptotic proteins, acquisition of epithelial-mesenchymal transition, and formation of cancer stem cells. MiRNAs mediate endocrine resistance through modulating ERα expression, receptor tyrosine kinase signaling, cell survival signaling, and apoptosis. Such emerging evidence indicates that miRNAs could be potential biomarkers for predicting a response to systemic therapy and prognosis in clinical settings. Targeting specific miRNAs of the drug-resistant network is promising in overcoming drug resistance in breast cancer.

摘要

乳腺癌是最常见的恶性肿瘤,也是女性癌症死亡的主要原因。耐药性是乳腺癌系统治疗的主要障碍,导致治疗失败、疾病失控和死亡。miRNAs 是癌症研究中的一个新兴领域。最近的证据表明,miRNAs 是乳腺癌耐药性的核心调节因子。临床前研究表明,miRNAs 通过上调药物外排转运蛋白和抗凋亡蛋白、获得上皮-间充质转化以及形成癌症干细胞,调节多药耐药信号转导网络。miRNAs 通过调节 ERα 表达、受体酪氨酸激酶信号、细胞存活信号和细胞凋亡来介导内分泌耐药。这些新出现的证据表明,miRNAs 可能成为预测临床治疗反应和预后的潜在生物标志物。针对耐药性网络中的特定 miRNAs 是克服乳腺癌耐药性的有前途的方法。

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