The introduction of EGFR-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment and prognosis of non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations. However, these patients display disease progression driven by the onset of acquired mechanisms of drug resistance that limit the efficacy of EGFR-TKI to no longer than one year. Moreover, a small fraction of EGFR-mutated NSCLC patients does not benefit from this targeted treatment due to primary (i.e. intrinsic) mechanisms of resistance that preexist prior to TKI drug treatment. Research efforts are focusing on deciphering the distinct molecular mechanisms underlying drug resistance, which should prompt the development of novel antitumor agents that surmount such chemoresistance modalities.

The capability of microRNAs (miRNAs) to regulate the expression of many oncogenic pathways and their central role in lung cancer progression, provided new directions for research on prognostic biomarkers, as well as innovative tools for predicting patients’ response to systemic therapies. Recent evidence suggests that modulation of key miRNAs may also reverse oncogenic signaling pathways, and potentiate the cytotoxic effect of anti-cancer therapies.

In this review, we focus on the putative emerging role of miRNAs in modulating drug resistance to EGFR-TKI treatment in EGFR-mutated NSCLC. Moreover, we discuss the current implications of miRNAs analyses in the clinical setting, using both tissue and liquid biopsies, as well as the future potential use of miRNA-based therapies in overcoming resistance to targeted agents like TKIs.

EGFR酪氨酸激酶抑制剂（TKIs）的引入彻底改变了具有表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者的治疗和预后。然而，这些患者表现出疾病的进展，这是由获得性耐药机制的出现所驱动的，这种机制将EGFR-TKI的疗效限制在一年以下。此外，一小部分EGFR突变的NSCLC患者由于原发性（即固有的抗药性机制，在TKI药物治疗之前就已经存在。研究工作集中在破译药物抗性的独特分子机制上，这将促使开发出超越此类化学抗药性的新型抗肿瘤药。

microRNA（miRNA）调节许多致癌途径的表达及其在肺癌进展中的核心作用的能力为预后生物标志物的研究提供了新的方向，并为预测患者对全身疗法的反应提供了创新的工具。最近的证据表明，关键miRNA的调节也可能逆转致癌信号通路，并增强抗癌疗法的细胞毒性作用。

在这篇综述中，我们集中于miRNA在调节EGFR突变的NSCLC中对EGFR-TKI治疗的耐药性中可能发挥的作用。此外，我们讨论了使用组织活检和液体活检进行miRNA分析在临床环境中的当前含义，以及基于miRNA的疗法在克服对TKI等靶向药物的耐药性方面的潜在潜在用途。