The Role of MicroRNAs as Predictors of Response to Tamoxifen Treatment in Breast Cancer Patients.
The Role of MicroRNAs as Predictors of Response to Tamoxifen Treatment in Breast Cancer Patients.
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DOI：
10.3390/ijms161024243
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发表时间：
2015-10-14
影响因子：
5.6
通讯作者：
Søiland H
中科院分区：
文献类型：
--
作者：
Egeland NG;Lunde S;Jonsdottir K;Lende TH;Cronin-Fenton D;Gilje B;Janssen EA;Søiland H
内分泌治疗是控制或根除乳腺癌的关键治疗策略。然而，对内分泌治疗的抵抗会导致乳腺癌复发。最近他莫昔芬辅助治疗延长至10年，这使得需要确定可用于监测治疗反应预测因子的生物标志物。microRNA是有前途的生物标志物，可以填补关于内分泌抵抗的临床前知识和临床观察之间的差距。microRNA通过转录后抑制或降解mRNA来调节基因表达，最常导致基因沉默。MicroRNA已被直接在原发性肿瘤中发现，但也在乳腺癌患者的循环中发现。研究患者中microRNA的少数可用研究表明，7种microRNA（miR-10a，miR-26，miR-30 c，miR-126 a，miR-210，miR-342和miR-519 a）在他莫昔芬耐药中发挥作用。独创性通路分析（IPA）表明，这七种microRNA与雌激素受体（ER）非依赖性通路的相互作用比与ER相关信号通路的相互作用更容易。这些途径中的一些是可靶向的（例如，PIK 3CA），提示microRNA作为内分泌抵抗的生物标志物可能具有临床价值。在大型前瞻性研究中验证这些候选microRNA的作用是必要的。
Endocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. However, resistance to endocrine therapy leads to breast cancer relapse. The recent extension of adjuvant tamoxifen treatment up to 10 years actualizes the need for identifying biological markers that may be used to monitor predictors of treatment response. MicroRNAs are promising biomarkers that may fill the gap between preclinical knowledge and clinical observations regarding endocrine resistance. MicroRNAs regulate gene expression by posttranscriptional repression or degradation of mRNA, most often leading to gene silencing. MicroRNAs have been identified directly in the primary tumor, but also in the circulation of breast cancer patients. The few available studies investigating microRNA in patients suggest that seven microRNAs (miR-10a, miR-26, miR-30c, miR-126a, miR-210, miR-342 and miR-519a) play a role in tamoxifen resistance. Ingenuity Pathway Analysis (IPA) reveals that these seven microRNAs interact more readily with estrogen receptor (ER)-independent pathways than ER-related signaling pathways. Some of these pathways are targetable (e.g., PIK3CA), suggesting that microRNAs as biomarkers of endocrine resistance may have clinical value. Validation of the role of these candidate microRNAs in large prospective studies is warranted.