Functional roles of exosomal miRNAs in multi-drug resistance in cancer chemotherapeutics.

Recent understanding of different molecular aspects of tumor initiation and progression has led to the discovery of a growing list of drugs. While these drugs have shown promising effects on tumor cells, their widespread usage has been hampered by the acquisition of drug resistance in a subpopulation of tumor cells. A differential pattern in the secretion of specialized vesicles named "exosomes" in drug-resistant cancer cells have recently received much attention. In addition, microRNAs (miRNAs) have been shown to be enriched in exosomes. Exosomal miRNAs (also known as exo-miRs) could be shuttled to recipient cells and play a role in the regulation of post-transcriptional gene expression, which may exert certain effects on cancer drug resistance. Here, we have reviewed the role of exo-miRs in chemotherapeutic resistance in different cancer types. Besides, studies which have focused on predictive role of circulating exo-miRs in cancer drug resistance are reviewed.

Mowla M ，Hashemi A 《-》

The role of exosomes and miRNAs in drug-resistance of cancer cells.

Chemotherapy, one of the principal approaches for cancer patients, plays a crucial role in controlling tumor progression. Clinically, tumors reveal a satisfactory response following the first exposure to the chemotherapeutic drugs in treatment. However, most tumors sooner or later become resistant to even chemically unrelated anticancer agents after repeated treatment. The reduced drug accumulation in tumor cells is considered one of the significant mechanisms by decreasing drug permeability and/or increasing active efflux (pumping out) of the drugs across the cell membrane. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated, including drug efflux, which is mediated by extracellular vesicles (EVs). Exosomes, a subset of EVs with a size range of 40-150 nm and a lipid bilayer membrane, can be released by all cell types. They mediate specific cell-to-cell interactions and activate signaling pathways in cells they either fuse with or interact with, including cancer cells. Exosomal RNAs are heterogeneous in size but enriched in small RNAs, such as miRNAs. In the primary tumor microenvironment, cancer-secreted exosomes and miRNAs can be internalized by other cell types. MiRNAs loaded in these exosomes might be transferred to recipient niche cells to exert genome-wide regulation of gene expression. How exosomal miRNAs contribute to the development of drug resistance in the context of the tumor microenvironment has not been fully described. In this review, we will highlight recent studies regarding EV-mediated microRNA delivery in formatting drug resistance. We also suggest the use of EVs as an advancing method in antiresistance treatment.

Bach DH ，Hong JY ，Park HJ ，Lee SK ... -  《-》

The emerging roles of exosomes in anti-cancer drug resistance and tumor progression: An insight towards tumor-microenvironment interaction.

The tumor microenvironment (TME) is a complex network of cellular organization consisting of fibroblasts, adipocytes, pericytes, immune cells endothelial cells, and extracellular matrix proteins. Besides communicating with each other, tumor cells are also involved in the tumor stroma interaction. Presently, most of the studies have focused on the contribution of TME in supporting tumor growth through intercellular communication by physical contact between the cells or through paracrine signaling cascades of growth factors and cytokines. The crosstalk between the tumor and TME has a pivotal role in the development of anti-cancer drug resistance. Drug resistance, be it against targeted or non-targeted drugs, has emerged as a major hurdle in the successful therapeutic intervention of cancer. Among the several mechanisms involved in the development of the resistance to anti-cancer therapies, exosomes have recently come into the limelight. Exosomes are the nano-sized vesicles, originated from the endolysosomal compartments and have the inherent potential to shuttle diverse biomolecules like proteins, lipids, and nucleic acids to the recipient cells. There are also instances where the pharmacological compounds are transferred between the cells via exosomes. For instance, the transfer of the cargoes from the drug-resistant tumor cells immensely affects the recipient drug-sensitive cells in terms of their proliferation, survival, migration, and drug resistance. In this review, we have discussed multiple aspects of the exosome-mediated bidirectional interplay between tumor and TME. Furthermore, we have also emphasized the contribution of exosomes promoting drug resistance and therapeutic strategies to mitigate the exosome induced drug resistance as well.

Jena BC ，Mandal M 《-》

Exosomes decrease sensitivity of breast cancer cells to adriamycin by delivering microRNAs.

Mao L ，Li J ，Chen WX ，Cai YQ ，Yu DD ，Zhong SL ，Zhao JH ，Zhou JW ，Tang JH ... -  《-》

The role of exosomes and "exosomal shuttle microRNA" in tumorigenesis and drug resistance.

How are intracellular proteins and nucleic acids transported to the appropriate sites, and how do they function at the proper time? This problem has plagued scientists for a long time. The roles of vesicles, and nanovesicles called exosomes, as carriers were revealed in 2013. Many types of cells can release exosomes, particularly tumor cells. Tumor-derived (TD) exosomes are rich in proteins and nucleic acids derived from parental cells. With the activity of signal transmission, these exosomes can guide communication between cells and induce cancer-related disorders in many signaling pathways. TD-exosomes can be a source of tumor antigen to induce an anti-tumor immune response but can also suppress the immune system. TD-exosomes are especially rich in microRNAs (miRNAs), which are in various pathological and physiological states. Therefore, exosomal miRNA can serve as a new diagnostic marker for cancers. Moreover, miRNAs in exosomes can shuttle between cells to communicate and exchange genetic material. Thus, TD-exosomes can be used as targeted therapies. Cell-type specificity, stability and accessibility from body fluids make exosomes valuable candidates for tumor diagnosis and targeted treatment.

Zhao L ，Liu W ，Xiao J ，Cao B ... -  《-》