Emerging strategies to overcome chemotherapy resistance in breast cancer

Chemotherapy resistance is a significant challenge in breast cancer (BC) treatment. Tumor cells adapt to standard therapies by activating drug efflux, enhancing DNA repair mechanisms, and modifying the tumor microenvironment. These adaptations limit the effectiveness of chemotherapy and contribute to cancer relapse. Combination therapies targeting multiple signaling pathways have improved initial responses in selected patients. However, resistance often develops, resulting in suboptimal outcomes. Immune-based treatments, especially for triple-negative breast cancer (TNBC), provide additional benefits but need further refinement to decrease toxicity and enhance patient selection. Nanotechnology introduces innovative delivery systems that co-administer chemotherapeutic agents alongside microRNAs or siRNAs using solid lipid carriers, non-ionic surfactant systems, and electrospun nanofibers. These advanced systems improve tumor targeting while reducing systemic toxicity. Additionally, chemosensitizers, such as pazopanib and 2-deoxy-D-glucose (2DG), help restore drug sensitivity by inhibiting resistance pathways. This review focuses on therapeutic approaches that tackle resistance in BC. It emphasizes the use of targeted combinations, nanocarrier-based systems, and chemosensitization. These strategies hold the potential for more effective and personalized treatments.