**4. Therapeutic implication of EVs in breast cancer**

The role of exosomes in carcinogenesis has been extensively investigated in recent years. Cancer cells have been shown to use exosomes as a novel mechanism to transfer the malignant phenotype to normal healthy cells and establish a niche for tumor growth. Cancer cell-derived exosomes are reported to contain miRNAs, proteins, or long non-coding RNAs that mediate cancer development, growth, and progression [42, 43].

#### *Engineering of Extracellular Vesicles as Nano Therapy for Breast Cancer DOI: http://dx.doi.org/10.5772/intechopen.101149*

Exosomes derived from breast cancer cells contain a variety of proteins and RNAs that are transmitted among these cells as well as normal cells, thus altering the phenotype of healthy mammary epithelial cells. Wang J et al. showed that cancer exosomes were able to transform normal mammary epithelial cells into cancerous cells via transfer of microRNAs packaged within exosomes [44]. Similarly, Melo et al. showed enhanced expression of exosomal miR-10b in metastatic breast cells compared to non-metastatic or non-malignant breast cells [45]. Thus, it can be used as a therapeutic target for breast cancer therapy.

These characteristics make exosomes ideal biomarkers, and exosomal profiling in the absence of tissue holds great promise for early diagnosis. Owing to their crucial functional role in breast cancer, exosomes have been investigated for their potential development as breast cancer biomarkers and therapeutic targets. Singh R et al. have shown that psoralen reduces the formation and secretion of exosomes, thus reversing multidrug resistance in breast cancer cells [46]. The presence of diverse content within and on the surface of exosomes has led to their application as biomarkers, diagnostics, and drug delivery. A large number of exosomes circulate within bodily fluids of not only healthy individuals but also cancer patients, according to some studies. Since exosomes play various significant roles in breast cancer, exosomes can be developed as potential therapeutic agents in biomarkers, diagnostics, and drug delivery. Kumar et al. investigated the release of exosomes from breast cancer stem cells to characterize their constituent exosomal markers. They detected tetraspanin proteins, Alix, and tumor susceptibility gene-101 (TSG101) in breast cancer stem cell-derived exosomes. This study indicates that secreted exosomes can be utilized as biomarkers for breast cancer to understand their development, progression, and metastasis [47]. Kumar et al. showed that miRNAs 155 and 205 are expressed in serum exosomes derived from breast cancer cells and modulate the epithelial-tomesenchymal transition (EMT), growth, and metastasis of cancer, suggesting their employability as breast cancer biomarkers [48]. Zhang et al. studied the role of long non-coding RNA MALAT 1 which is highly expressed in exosomes derived from breast cancer cells in tumor progression, representing a potential treatment strategy for breast cancer [49]. Dong et al. investigated the role of exosomal long non-coding RNA in the chemoresistance of HER2+ breast cancer cells. They found that exosomal lncRNA-SNHG14 was not only upregulated in trastuzumab-resistant cells but also transmitted the lncRNA into drug-sensitive cells, thus disseminating trastuzumab resistance. Furthermore, when compared to patients who responded to trastuzumab, the expression level of serum exosomal lncRNA-SNHG14 was higher in patients who were resistant. This suggests that lncRNA-SNHG14 is a promising therapeutic target for HER2+ breast cancer patients [50].
