Potential roles and prognostic significance of exosomes in cancer drug resistance

Abstract

Drug resistance is a major impediment in cancer therapy which strongly reduces the efficiency of anti-cancer drugs. Exosomes are extracellular vesicles with cup or spherical shape with a size range of 40-150 nm released by eukaryotic cells that contain genetic materials, proteins, and lipids which mediate a specific cell-to-cell communication. The potential roles of exosomes in intrinsic and acquired drug resistance have been reported in several studies. Furthermore, a line of evidence suggested that the content of exosomes released from tumor cells in biological samples may be associated with the clinical outcomes of cancer patients. In this review, we highlighted the recent studies regarding the potential roles of exosomes in tumor initiation, progression, and chemoresistance. This study suggests the possible role of exosomes for drug delivery and their contents in prognosis and resistance to chemotherapy in cancer patients.

Keywords: Biomarker; Chemoresistance; Extracellular vesicles; MicroRNAs; Tumor microenvironment.

Fig. 1

a Exosomes are cup/spherical-shaped vesicles (40–150 nm) with a double-layered lipid membrane surrounding a small cytosol without any organelles. This phospholipid bilayer membrane loaded with peripheral and integral proteins. Exosomes also contain nucleic acids (e.g. DNA, mRNAs, microRNAs, and long non-coding RNAs) and lipids. b Exosome biogenesis started via endocytosis pathway and early endosome formation. During this process, the cell membrane components (proteins and etc.) are embedded into the early endosomes’ membrane, which then matured into late endosomes. Inward budding of late endosomal membrane creates multiple intraluminal vesicles (ILVs) within multivesicular endosomes, in which some particular proteins and other cytosolic constituents are enveloped in exosomes under control of ESCRT family. MVBs then fuse with the cell membrane to release their ILVs into extracellular milieu by Rab GTPases 27A and B molecular motors

Fig. 2

Exosome mediated cancer drug resistance mechanisms