Emerging roles of exosomal miRNAs in breast cancer drug resistance

Abstract

Breast cancer (BC), as a heterogeneous disease, is considered as one of the most common malignancies in women worldwide. The resistance of BC cells to therapeutic agents has remained a big challenge in the treatment of BC patients. Some factors such as cytokines, exosomes, and soluble receptors were recognized as crucial agents involved in the development of drug resistance. However, the exact mechanisms underlying the drug resistance is still unknown. There is growing evidence to support the emerging roles of exosomes, especially exosomal miRNAs, in tumor initiation, angiogenesis, proliferation, migration, invasion, metastasis, and drug resistance. Therefore, identification of BC-specific exosomal miRNAs and their underlying mechanisms would be helpful to define sensitivity to therapeutic drugs and establish an appropriate therapeutic strategy. This review focuses mainly on the roles of exosomal miRNAs and their associated mechanisms in the resistance of BC cells to therapeutic agents, as well as critically examines the potential of these macromolecules as a treatment biomarker in BC patients. K E Y W O R D Sbreast cancer, exosomes, drug resistance, therapeutics, exosomal miRNA, microRNA 1 | INTRODUCTION Breast cancer (BC), after skin cancer, was reported to be the most common malignancy in women worldwide. 1 Conversely, BC was showed to have a low incidence rate in men, approximately 1%. BC does not kill in primary stage. It was shown that the 5-year survival rates are 99%, 84%, and 23% for women with localized BC, regional stage, and

How hypoxia regulate exosomes in ischemic diseases and cancer microenvironment?

“…As discussed earlier, increased oxygen consumption and demands due to the high proliferation rate of tumor cells, as well as irregular new vascular networks lead to a hypoxic TME in solid tumors . Tumor cells respond to hypoxic stress by secretion of exosomes containing especial macromolecules with the ability to modulate angiogenesis and tumor fate . For example, a significant increase in the exosomal miRNA‐210 of hypoxic breast cancer cells was observed both in vitro and in vivo.…”

“…As discussed earlier, exosomes have multifunctional roles in normal and diseased conditions. For examples, miRNAs and some other macromolecules in exosomes can mediate cell behaviors (proliferation, migration, differentiation, and function), tumor resistance, progression, metastasis, and prognosis . Exosomes can also be considered as a biomarker in hypoxia‐associated disorders such as MI, stroke, and pre‐eclampsia .…”

“…Exosomes have multifunctional roles in cell–cell and cell‐matrix communications, regulation of cell behavior, and others. For examples, the regulatory functions of exosomes were found to play a role in initiation, proliferation, invasion, metastasis, and even resistance of cancer cells to therapeutic agents . It is well‐known that exosome compositions can be altered in normal and diseased conditions .…”

“…For examples, the regulatory functions of exosomes were found to play a role in initiation, proliferation, invasion, metastasis, and even resistance of cancer cells to therapeutic agents . It is well‐known that exosome compositions can be altered in normal and diseased conditions . Although some studies reported that the change in pH, temperature, oxidative stress, hypoxia, radiation, and shear stress can affect the secretion level and composition of exosomes, the exact mechanisms by which the secretion, content, and functions of exosomes are regulated are still not well elucidated .…”

Epigenetic Drugs for Cancer and microRNAs: A Focus on Histone Deacetylase Inhibitors

“…Interestingly, this miRNA participates in the p53 network [147] and is frequently upregulated or mutated in cancers [148,149]. To our knowledge, this is the only study about the use of circulating miRNAs as a prognostic biomarker of HDACi response, even if it is a conventional approach for other anti-tumor treatments, as recently described in the review of Najminejad et al [150] and Pardini et al [151]. We believe however, that it can be a promising approach since miRNAs are stable and easily detectable in all body fluids.…”