Bridging molecular insights and clinical application: non-coding RNAs, targeted drug delivery, and metastatic breast cancer therapy.

Breast cancer (BC) is one of the most common types of malignancy diagnosed globally. Metastasis plays a major role in most of the cancer-related mortality among affected patients. Despite the advances in the areas of early detection and localized treatment modalities, there prevail several challenges which the therapeutic strategies encounter, like drug resistance, tumor heterogeneity, and drug delivery. This review presents a comprehensive and detailed overview of organ-specific metastasis that occur in BC, specifically emphasizing key sites such as the bone, liver, lung, and brain. It also outlines the significance of various therapies like chemotherapies, endocrine therapies, targeted therapies and immunotherapies that have been clinically approved to date. The review specifically emphasizes the molecular mechanisms by which non-coding RNAs (ncRNAs) act to exert their effects in regulating drug resistance. It also addresses the new advances in nanotechnology-based drug delivery systems (DDS) that function to enhance the specificity of treatments while simultaneously reducing systemic toxicity. Beyond ncRNAs, this review also explores other critical mechanisms of drug resistance in metastatic BC, including efflux transporter activity, target gene mutations, and micro-environmental factors, to mention a few. Moreover, the review also discusses the clinical significance of combination therapies and new therapeutic strategies, including the use of repurposed drugs and the concepts of personalized medicine. A greater understanding of the ncRNA-mediated signaling pathways, in combination with the latest advances in drug delivery systems, has the potential to greatly improve therapeutic efficacy and could result in more favorable clinical outcomes in the treatment of metastatic BC (MBC).