**6. Exosomes in chemotherapy and other therapy**

Chemo-resistance should be solved for effective cancer therapy. Several studies indicated that signal transducer and activator of transcription 3 (STAT3), focal adhesion kinase (FAK) and epithelial-mesenchymal transition (EMT) contribute to the development of chemotherapeutic resistance [88–91]. The anti-apoptotic signal which is activated by the STAT3 pathway is an important factor in causing initial drug resistance [88]. FAK is reported to promote invasive tumor growth with β-catenin [89]. EMT is popular with the induction of cancer metastasis [90], but it is also deeply related to drug resistance. Mani et al. reported that EMT may cause cancer cells to acquire epithelial stem cell properties [91]. EMT formation induces chemo-resistance [92] and it is induced by various signaling pathways, such as TGFβ, Wnt signal, etc. [93, 94].

Several studies have demonstrated that exosomal activity might be involved in chemo-resistance. In EMT, Shan et al. indicated that downregulation of exosomal miR-148b-3p may offer opportunities in the treatment of bladder cancer by increasing chemosensitivity via inhibition of the Wnt/β-catenin pathway and promoting expression of PTEN [95]. In addition to it, Liu et al. reported that exosome-transmitted miR-128-3p increased chemosensitivity of oxaliplatin-resistant colorectal cancer by suppressing epithelial-mesenchymal transition and inducing drug accumulation in cancer cells [96]. Furthermore, exosomes derived from cancer-associated fibroblasts and cancer cells are often reported to contribute to chemo-resistance [97, 98]. According to these reports, exosomes are also important to the regulation of chemotherapy.
