Abstract
Extracellular vesicles are small membrane particles derived from various cell types. EVs are broadly classified as ectosomes or small extracellular vesicles, depending on their biogenesis and cargoes. Numerous studies have shown that EVs regulate multiple physiological and pathophysiological processes. The roles of small extracellular vesicles in cancer growth and metastasis remain to be fully elucidated. As endogenous products, small extracellular vesicles are an ideal drug delivery platform for anticancer agents. However, several aspects of small extracellular vesicle biology remain unclear, hindering the clinical implementation of small extracellular vesicles as biomarkers or anticancer agents. In this review, we summarize the utility of cancer-related small extracellular vesicles as biomarkers to detect early-stage cancers and predict treatment outcomes. We also review findings from preclinical and clinical studies of small extracellular vesicle-based cancer therapies and summarize interventional clinical trials registered in the United States Food and Drug Administration and the Chinese Clinical Trials Registry. Finally, we discuss the main challenges limiting the clinical implementation of small extracellular vesicles and recommend possible approaches to address these challenges.
Highlights
Extracellular vesicles (EVs) are small lipid bilayer-bound vesicles released from living cells into the extracellular environment
We focus on the recent development of small extracellular vesicles (sEVs) as biomarkers for early cancer detection and follow-up care, as well as therapeutic particles for cancer treatment
Since most RNAs are relocated to specific cellular compartments in association with RNA-binding proteins (RBPs) and 25% of sEV proteins have been identified as RBPs, it is rational to assume that RBPs are important in transferring RNAs into sEVs [35, 36]
Summary
Extracellular vesicles (EVs) are small lipid bilayer-bound vesicles released from living cells into the extracellular environment. Each sEV group demonstrated distinct oncogenic functions; for instance, doxorubicin-elicited sEVs enhanced melanoma cell migration, and oxidative stress-elicited sEVs promoted Ki-67 upregulation in mesenchymal stem cells [60] These results suggest that we may be able to predict therapeutic outcomes and design more effective personalized cancer treatment plans based on the analysis of sEVs from the patients’ tumor tissue, organoid models, or xenograft models. Guo et al discovered that the autophagy-related protein 5 (ATG5) could improve sEV secretion by dissociating V1V0-ATPase that acidifies MVBs and lysosomes, similar to the mechanism that bafilomycin A1 promoted sEV secretion; the increased sEV secretion could accelerate tumor migration in breast cancer mice models [84] These conflicting results may be due to the relatively small sample size of animal experiments, different cell types, and more importantly, the intricate relationship between sEV secretion and autophagy, warranting extensive investigation to illuminate the underlying mechanism.
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