The potential diagnostic, prognostic, and therapeutic role of extracellular vesicles in breast cancer

Triple negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer characterized by high aggressiveness, metastasis, relapse, and poor prognosis. Furthermore, it is unresponsive to hormone and targeted therapies. The tumor microenvironment (TME) plays a crucial role in driving tumor progression by providing oxygen and nutriment supply and intercellular communicators such as extracellular vesicles (EVs). EVs are membrane-bound structures shed by nearly all cell types and involved in both physiological and pathological processes. EVs deliver multiple functional cargos including proteins, lipids, and nucleic acids. Moreover, EV content acts as pivotal mediator of cell behaviors. Due to their promising potential, EVs have been extensively investigated as biomarkers for diagnostic, prognostic and therapeutic purposes. Emerging evidence confirms that EVs isolated from TNBC cells are able to transfer oncogenic signal and drug resistance to non-tumorigenic breast cells. Furthermore, it has been demonstrated that annexin A6 enclosed in TNBC cells-derived EVs induces gemcitabine resistance. Therefore, EVs may be a reliable predictor of tumor cell response to therapies. The lack of approved therapies for TNBC patients highlights the need for new therapeutic approaches, and engineered EVs can represent a potential TNBC therapeutic option.