Research on exosomes in cancer multidrug resistance and clinical translation

Multidrug resistance (MDR) is a major clinical challenge that limits the efficacy of multiple cancer treatment modalities, including chemotherapy, targeted therapy, immunotherapy, monoclonal antibody therapy, and antibody-drug conjugates. In recent years, exosomes (Exos), nanoscale vesicles involved in intercellular communication, have attracted increasing attention for their roles in the formation and spread of MDR. A growing body of evidence suggests that Exos mediate the transfer of resistance-related molecular signals among drug-resistant cancer cells, drug-sensitive cancer cells, and stromal cells, such as cancer-associated fibroblasts and tumor-associated macrophages, through the selective packaging of noncoding RNAs, functional proteins, and metabolic regulators. These molecular signals may induce the reprogramming of signaling pathways, metabolism, and epigenetic states in recipient cells, thereby promoting the acquisition of cancer stem cell-like properties and a drug-resistant phenotype. In turn, these changes may contribute to the establishment of a drug resistance-supporting tumor microenvironment. This review systematically summarizes the molecular mechanisms by which Exos contribute to multidrug resistance, with a particular focus on their roles in cargo sorting, microenvironmental crosstalk, and the functional reprogramming of recipient cells. It also discusses their potential for clinical translation in resistance monitoring and reversal therapy. In addition, this review further discusses the key challenges currently facing the field and provides perspectives on future research directions.