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MiRNAs与EGFR-TKIs继发性耐药机制的研究进展

         

摘要

肺癌是癌症致死率最高的疾病,关于这个疾病的发生机制已得到部分阐明,其中表皮生长因子受体(epidermal growth factor receptor, EGFR)信号通路研究最为深入,在肺癌的发生中起着至关重要的作用。而有效地抑制EGFR信号通路的药物已用于非小细胞肺癌(non-small cell lung cancer, NSCLC)的靶向治疗中,伴有EGFR基因突变的患者使用EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors, EGFR-TKIs)治疗后获得不错的临床收益,但大部分患者在使用该药治疗10个月后出现耐药现象。MiRNAs(microRNAs)是一种非编码蛋白的RNA,参与转录后水平基因的表达调控。越来越多的研究发现miRNAs与EGFR-TKIs继发性耐药有关,miRNAs可作为逆转EGFR-TKIs耐药及评估EGFR-TKIs有效性的生物指标。本文就NSCLC中miRNAs与EGFR-TKIs继发性耐药机制之间的相关性研究进展做简要的综述。%Lung cancer is a leading cause of cancer mortality worldwide. Several molecular pathways underlying mechanisms of this disease have been partly elucidated, among which the epidermal growth factor receptor (EGFR) pathway is one of the well-known signaling cascades that plays a critical role in tumorigenesis. hTe strategies to effectively inhibit EGFR signaling pathway have been used in non-small cell lung cancer (NSCLC) targeted therapy. Patients withEGFR mutations beneift fromEGFR-tyrosine kinase inhibitors (EGFR-TKIs) treatment. However, most of TKIs-treated patients eventually suffer drug resistant atfer 10-month treatments. MiRNAs (microRNAs) is a non coding RNA and protein involved in regulating gene expression in the transcription level. More and more studies have found that miRNAs are correlated with EGFR-TKIs second-ary resistance. MiRNAs may serve as novel targets to circumvent the resistance and promising predictive biomarkers for EGFR-TKIs. In this paper, we reviewed brielfy advanced research on miRNAs and EGFR-TKIs secondary resistance in NSCLC.

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