Targeting drug resistance in breast cancer: the potential of miRNA and nanotechnology-driven delivery systems

Breast cancer is the second leading cause of cancer-related deaths in females worldwide. Despite significant advancements in treatment, drug resistance remains a major challenge, limiting the effectiveness of therapies and leading to dismal outcomes. Approximately 50% of HER2+ breast cancer patients develop resistance to trastuzumab, and patients with triple-negative breast cancer often experience resistance to first-line therapies. The drug resistance mechanisms involve altered drug uptake, enhanced DNA repair, and dysregulated apoptosis pathways. MicroRNAs are essential in regulating cellular processes involved in both homeostasis and disease. Recent data suggest that microRNAs can overcome drug resistance by regulating the pathways that confer drug resistance. Combining different conventional anticancer agents with microRNA therapies holds promise for enhancing treatment effectiveness against drug resistant breast cancer. Advancements in nano-drug delivery systems have facilitated the effective delivery of microRNAs by improving their stability, targeting specific cells, and enhancing cellular uptake. This review elucidates the recent advancements in microRNA-based therapies, their effects on gene expression, and their clinical efficacy in overcoming drug resistance in breast cancer.