# Extracellular Vesicles and Artificial Intelligence: Unique Weapons against Breast Cancer
## 2 EVs in Breast Cancer  
An EV's cargo is transferred from a parent cell to a recipient cell, so it is subsequently involved in tumor initiation and progression, metastasis formation via the dissemination of the oncogene in target cells, and remodeling the extracellular matrix [48; 49; 50; 51; 52]. The involvement of TEVs in BC has been reported in the literature for many years. In 2013, exosomes derived from the triple-negative breast cancer (TNBC) Hs578 Ts(i)8 cell line were investigated, and their increased invasiveness in the recipient cells utilized was noted; for example, TNBC patients' exosomes derived from sera were able to transfer phenotypic traits from the original cells to the receiving cells [53]. Certain authors have highlighted the role of exosomal miR-10b in tumoral invasiveness in the metastatic breast cancer MDA-MB-231 cell line [54]. Similar results were obtained for cancer-secreted miR-105, which regulated and induced cell migration via exosome-mediated transfer [55]. Tumor progression was investigated in response to hypoxic conditions; in particular, among the exosomal miRNAs, miR-16, let7a, miR-21, and miR-210 secreted by the MDA-MB-231 and T47D breast cancer cell lines, the latter was found to be significantly upregulated in hypoxic conditions and is thus a good target for a therapeutic approach [56]. Through the expression of peculiar exosomal integrins, exosomes can influence tumor cells' tropism to enable metastases (integrins \(\alpha\)6\(\beta\)4 and \(\alpha\)6\(\beta\)1 are associated with pulmonary metastases, while \(\alpha\)v\(\beta\)5 is associated with liver metastases) [57]. Due to their own tendencies to be intrinsically biologically active and not only vectors of information, it has also been demonstrated that some precursor microRNAs (pre-miRNAs) present in BC-derived TEVs were processed into mature miRNAs within TEVs in a cell-independent manner. On the other hand, BC-EVs derived from the cells and sera of patients induced nontumorigenic epithelial cells to cause cancer in a Dicer-dependent manner, promoting tumorigenesis [57]. As shown in the current literature, the role of mesenchymal stem cells (MSCs) is gaining significant interest, and the results are often controversial, sometimes showing pro-tumor activity while demonstrating the opposite role in other cases [58]. In 2014, [PERSON] et al. demonstrated that the coculture of a bone marrow metastatic human breast cancer cell line (BM2) with human donor-derived bone marrow mesenchymal stem cells (BM-MSCs) induced the acquisition of dormant phenotypes in the BM2 cells, causing unresponsiveness to traditional chemotherapy approaches. The same effect was achieved by culturing the cells with exosomes isolated from BM-MSC cultures. This evidence, together with the overexpression of miR-23b in BM-MSC-derived exosomes, suggests the role of exosomes in promoting BC cell dormancy in the metastatic niche [59]. Researchers demonstrated the anti-angiogenic effect of MSC-derived exosomes enriched in miR-16, which target vascular endothelial growth factor (VEGF) with a consequent inhibition of angiogenesis [60]. Some reported higher levels of circulating exosomal miR-373 in triple-negative carcinomas than in luminal carcinomas, such as in estrogen-negative and progesterone-negative tumors, suggesting a correlation of this exosomal miR-RNA with the aggressiveness of breast carcinomas [61]. Other authors demonstrated that BC-EVs could carry miR-182-5p, which is highly expressed in breast cancer tissues and cells, and were able to downregulate CKLF-like MARVEL transmembrane domain-containing 7 (CMTM7) expression and activate the EGFR/AKT signaling pathway, with a consequent aggravation of breast cancer and the promotion of breast cancer angiogenesis through EVs-miR-182-5p [62; 63]. In 2022, [PERSON] et al.