Exosomes and their role in tumorigenesis and anticancer drug resistance

Abstract

Exosomes are a class of extracellular vesicles ranging in size from 40 to 100 nm, which are secreted by both cancer cells and multiple stromal cells in the tumor microenvironment. Following their secretion, exosomes partake in endocrine, paracrine and autocrine signaling. Internalization of exosomes by tumor cells influences several cellular pathways which alter cancer cell physiology. Tumor-derived exosomes secreted by cancer or stromal cells can also confer anticancer drug-resistant traits upon cancer cells. These exosomes promote chemoresistance by transferring their cargo which includes nucleic acids, proteins, and metabolites to cancer cells or act as a decoy for immunotherapeutic targets. Depletion of exosomes can reverse some of the detrimental effects on tumor metabolism and restore drug sensitivity to chemotherapeutic treatment. Herein we discuss various approaches that have been developed to deplete exosomes for therapeutic purposes. The natural composition, low immunogenicity and cytotoxicity of exosomes, along with their ability to specifically target tumor cells, render them an appealing platform for drug delivery. The ability of exosomes to mediate autocrine and paracrine signaling in target cells, along with their natural structure and low immunogenicity render them an attractive vehicle for the delivery of anticancer drugs to tumors.

Keywords: Drug delivery; Drug resistance; Exosomes; Tumor microenvironment.