Extracellular Vesicles: Emerging Modulators of Cancer Drug Resistance

SIMPLE SUMMARY: Drug resistance still represents the main reason for therapy failure in cancer patients. In the last decade, extracellular vesicles (EVs), a heterogeneous group of particles implicated in cell-to-cell communication, have been shown to substantially contribute to this phenomenon. This review summarizes the molecular mechanisms underlying the EV-mediated development of chemoresistance, shedding light on the potential role of these vesicles as both diagnostic/prognostic markers and therapeutic targets. ABSTRACT: Extracellular vesicles (EVs) have recently emerged as crucial modulators of cancer drug resistance. Indeed, it has been shown that they can directly sequester anti-tumor drugs, decreasing their effective concentration at target sites. Moreover, they facilitate the horizontal transfer of specific bioactive cargoes able to regulate proliferative, apoptotic, and stemness programs in recipient cells, potentially conferring a resistant phenotype to drug-sensitive cancer cells. Finally, EVs can mediate the communication between the tumor and both stromal and immune cells within the microenvironment, promoting treatment escape. In this context, clarifying the EV-driven resistance mechanisms might improve not only tumor diagnosis and prognosis but also therapeutic outcomes. Detailed cellular and molecular events occurring during the development of EV-mediated cancer drug resistance are described in this review article.