Abstract

Breast cancer remains a leading lethal cancer in women globally, with the HER2+ positive subtype associated with a higher chance of therapeutic resistance. Treatments tailored specifically to this subtype, such as targeted therapies, have significantly developed over the past decade. However, the issue of drug resistance to targeted drugs underlines the necessity of better treatment approaches. Recent studies have focused on microRNAs (miRNAs), single-stranded non-coding RNAs, as critical regulators in drug resistance mechanisms. These miRNAs, capable of influencing various cellular processes, have emerged as critical modulators in numerous diseases, including different cancer types, particularly breast cancer. This article reviews current methodologies in the study of miRNAs within the context of HER2-positive breast cancer, from the selection of study models and sample extraction to comprehensive analysis methods. Our objective is to highlight the potential that miRNAs hold as biomarkers capable of regulating drug resistance in this specific cancer subtype. Moreover, we also discuss the importance of integrating advanced study models alongside the latest bioinformatics tools to enrich this research domain. Furthermore, this article evaluates the use of clinical samples and cell line models for studying miRNAs in this field, outlining the advantages and limitations of each method and proposing a refined approach to research design. The main contribution of this work is the establishment of a detailed taxonomy of research strategies that address current challenges while also outlining promising future directions, particularly focused on elucidating the regulatory mechanisms of miRNAs in therapeutic resistance in breast cancer. In addition, by underscoring the necessity of employing a diverse array of study models and capitalizing on bioinformatics advancements, this article seeks to uncover the complex interactions between miRNAs and drug resistance mechanisms in breast cancer. Ultimately, our goal is to pave the way toward overcoming therapeutic resistance, thereby improving the prognosis for patients afflicted with HER2-positive breast cancer.

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