HER2-low breast cancer has been recognized as a heterogenous group of tumors influenced by hormone receptor (HR) expression, giving rise to tumors with either a luminal-like phenotype or features resembling triple-negative breast cancer (TNBC). Despite the development of HER2-targeted therapies, several studies have demonstrated their limited efficacy in patients diagnosed with HER2-low breast cancer. However, recent research has led to the development of antibody-drug conjugates (ADCs), such as trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), with the latter showing promising results in treating these patients. Despite this breakthrough, the availability of a single effective therapy fails to account for tumor heterogeneity and may contribute to the emergence of therapy resistance, leaving HER2-low patients without treatment options. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at a post-transcriptional level and are capable of modulating key cellular processes. Recent studies have highlighted their potential as therapeutic targets, contributing to the advancement of personalized, patient-center therapies. In this context, the interplay between miRNAs and HER2-targeted therapies, particularly their modulation of common essential genes and signaling pathways, could reshape HER2-low therapy strategies to transform current practices aimed at improving the overall patient outcomes. Therefore, this review aims to elucidate the mechanisms underlying current HER2-targeted therapy and explore a potential crosstalk with miRNAs, ultimately serving as a guide for the development of personalized therapeutic strategies.
HER2低表达乳腺癌已被确认为一类异质性肿瘤，其特性受激素受体表达状态影响，可呈现管腔样表型或类似三阴性乳腺癌的特征。尽管HER2靶向治疗不断发展，多项研究表明其对HER2低表达乳腺癌患者的疗效有限。近年来抗体偶联药物的研发取得突破性进展，如恩美曲妥珠单抗和德曲妥珠单抗，其中后者在该类患者的治疗中展现出显著潜力。然而，单一有效疗法的局限性在于无法应对肿瘤异质性，可能导致耐药性产生，致使HER2低表达患者面临治疗选择匮乏的困境。 微小RNA作为在转录后水平调控基因表达的非编码小分子RNA，能够调节关键细胞进程。最新研究揭示了其作为治疗靶点的潜力，为推进个体化、以患者为中心的治疗策略提供了新方向。在此背景下，微小RNA与HER2靶向治疗的相互作用——特别是其对共同必需基因和信号通路的调控机制——可能重塑HER2低表达乳腺癌的治疗策略，推动现有临床实践向改善患者整体预后的方向转型。本综述旨在阐明当前HER2靶向治疗的作用机制，探索其与微小RNA的潜在交互关系，最终为开发个体化治疗策略提供理论依据。
肿瘤(癌症)患者之家