Abstract

Extracellular vesicles (EVs) are small lipid bilayer-delimited nanoparticles released from all types of cells examined thus far. Several groups of EVs, including exosomes, microvesicles, and apoptotic bodies, have been identified according to their size and biogenesis. With extensive investigations on EVs over the last decade, it is now recognized that EVs play a pleiotropic role in various physiological processes as well as pathological conditions through mediating intercellular communication. Most notably, EVs have been shown to be involved in cancer initiation and progression and EV signaling in cancer are viewed as potential therapeutic targets. Furthermore, as membrane nanoparticles, EVs are natural products with some of them, such as tumor exosomes, possessing tumor homing propensity, thus leading to strategies utilizing EVs as drug carriers to effectively deliver cancer therapeutics. In this review, we summarize recent reports on exploring EVs signaling as potential therapeutic targets in cancer as well as on developing EVs as therapeutic delivery carriers for cancer therapy. Findings from preclinical studies are primarily discussed, with early phase clinical trials reviewed. We hope to provide readers updated information on the development of EVs as cancer therapeutic targets or therapeutic carriers.

Highlights

  • Extracellular vesicles (EVs) are a generic term referring to several groups of small lipid bilayer-delimited particles generated through various cellular processes and released from all types of cells investigated far

  • The involvement of EVs, especially small EVs (sEVs), in promoting cancer progression through intercellular communication is well recognized. This leads to efforts focusing on targeting EV signaling or utilizing EVs as drug carriers to develop novel cancer therapeutics

  • We have summarized recent progress in the development of EVs as cancer therapeutics, both in preclinical studies and clinical trials

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Summary

Introduction

Extracellular vesicles (EVs) are a generic term referring to several groups of small lipid bilayer-delimited particles generated through various cellular processes and released from all types of cells investigated far. These membrane vesicles, including microvesicles ( known as microparticles or ectosomes), exosomes, and apoptotic bodies, all lack a functional nucleus and are unable to replicate themselves. We will focus on recent work in the development of cancer therapeutics targeting EV-mediated cellular processes or utilizing EVs as vehicles for drug delivery. A simplified view of general aspects of EVs is provided at the first section of this review

EV Nomenclature
EV Surface Markers and Cargos
EV Functions
EVs as Potential Therapeutic Targets in Cancer
Suppressing sEV Biogenesis and Release
Preventing EV Uptake
Targeting Specific sEV Cargo Components
EVs as Drug Carriers in Cancer Treatment
EV Sources and Loading Efficiency
Loading Therapeutics into sEVs via Donor Cells
Loading Therapeutics into Isolated sEVs
Clinical Trials Testing sEVs as Cancer Therapeutic Carriers
Clinical Trials Using Tumor Cell-Derived EVs
Clinical Trials Using Normal Fibroblast-Like Mesenchymal Cell-Derived EVs
Findings
Conclusions
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