ABC Transporter Protein-mediated Multidrug Resistance in Breast Cancer and Development of Targeting Strategies

Drug resistance (MDR) poses a significant challenge in breast cancer (BrCa) treatment, resulting in reduced efficacy and increased tumor recurrence. Resolving MDR in BrCa is necessary for improving the clinical efficacy of antitumor therapy. However, the molecular mechanisms underlying MDR are complex and involve various biological processes, including ABC drug transporter-mediated drug efflux, abnormal drug metabolism, and the development of the tumor microenvironment. The abnormal expression of ABC transporter proteins constitutes a critical mechanism driving MDR in BrCa. Factors like breast cancer stem cells (BCSCs), epigenetic changes, cell membrane lipids, and microenvironmental components affect the expression and function of ABC transporter proteins in BrCa. Here, we focus on the roles of Pglycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP) in relation to MDR. Additionally, we review the factors affecting the expression and function of these transporters, emphasizing strategies such as gene modification, drug development, and modulation of cell membrane lipids.