EZH2 as a new therapeutic target in brain tumors: Molecular landscape, therapeutic targeting and future prospects

Extracellular vesicles (EVs) are a group of communication organelles enclosed by a phospholipid bilayer, secreted by all types of cells. The size of these vesicles ranges from 30 to 1000 nm, and they contain a myriad of compounds such as RNA, DNA, proteins, and lipids from their origin cells, offering a good source of biomarkers. Exosomes (30 to 100 nm) are a subset of EVs, and their importance in future medicine is beyond any doubt. However, the lack of efficient isolation and detection techniques hinders their practical applications as biomarkers. Versatile and cutting-edge platforms are required to detect and isolate exosomes selectively for further clinical analysis. This review paper focuses on lab-on-chip devices for capturing, detecting, and isolating extracellular vesicles. The first part of the paper discusses the main characteristics of different cell-derived vesicles, EV functions, and their clinical applications. In the second part, various microfluidic platforms suitable for the isolation and detection of exosomes are described, and their performance in terms of yield, sensitivity, and time of analysis is discussed.

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Microfluidic Platforms for the Isolation and Detection of Exosomes: A Brief Review

Hepatocellular carcinoma (HCC) is the most common malignancy of hepatocytes accounting for 75-85% of primary hepatic carcinoma cases. Small extracellular vesicles (sEVs), previously known as exosomes with a diameter of 30-200 nm, can transport a variety of biological molecules between cells, and have been proposed to function in physiological and pathological processes. Recent studies have indicated that the cargos of sEVs are implicated in intercellular crosstalk among HCC cells, paratumor cells and the tumor microenvironment. sEV-encapsulated substances (including DNA, RNA, proteins and lipids) regulate signal transduction pathways in recipient cells and contribute to cancer initiation and progression in HCC. In addition, the differential expression of sEV cargos between patients facilitates the potential utility of sEVs in the diagnosis and prognosis of patients with HCC. Furthermore, the intrinsic properties of low immunogenicity and high stability render sEVs ideal vehicles for targeted drug delivery in the treatment of HCC. The present review article summarizes the carcinogenic and anti-neoplastic capacities of sEVs and discusses the potential and prospective diagnostic and therapeutic applications of sEVs in HCC.

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Roles of small extracellular vesicles in the development, diagnosis and possible treatment strategies for hepatocellular carcinoma (Review)

Cancer stem cells (CSCs) represent a small portion of tumor cells with self-renewal ability in tumor tissues and are a key factor in tumor resistance, recurrence, and metastasis. CSCs produce a large number of exosomes through various mechanisms, such as paracrine and autocrine signaling. Studies have shown that CSC-derived exosomes (CSC-Exos) carry a variety of gene mutations and specific epigenetic modifications indicative of unique cell phenotypes and metabolic pathways, enabling exchange of information in the tumor microenvironment (TME) to promote tumor invasion and metastasis. In addition, CSC-Exos carry a variety of metabolites, especially proteins and miRNAs, which can activate signaling pathways to further promote tumor development. CSC-Exos have dual effects on cancer development. Due to advances in liquid biopsy technology for early cancer detection, CSCs-Exos may become an important tool for early cancer diagnosis and therapeutic drug delivery. In this article, we will review how CSC-Exos exert the above effects based on the above two aspects and explore their mechanism of action.

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The Role of Cancer Stem Cell-Derived Exosomes in Cancer Progression

Exosomes are biological nanoscale spherical lipid bilayer vesicles, 40–160 nm in diameter, produced by most mammalian cells in both physiological and pathological conditions. Exosomes are formed via the endosomal sorting complex required for transport (ESCRT). The primary function of exosomes is mediating cell-to-cell communication. In terms of cancer, exosomes play important roles as mediators of intercellular communication, leading to tumor progression. Moreover, they can serve as biomarkers for cancer detection and progression. Therefore, their utilization in cancer therapies has been suggested, either as drug delivery carriers or as a diagnostic tool. However, exosomes were also reported to be involved in cancer drug resistance via transferring information of drug resistance to sensitive cells. It is important to consider the current knowledge regarding the role of exosomes in cancer, drug resistance, cancer therapies, and their clinical application in cancer therapies.

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The Role of Exosomes in Human Carcinogenesis and Cancer Therapy—Recent Findings from Molecular and Clinical Research

Exosomes are very small extracellular vesicles secreted by multiple cell types and are extensively distributed in various biological fluids. Recent research indicated that exosomes can participate in regulating the tumor microenvironment and impacting tumor proliferation and progression. Due to the extensive enrollment in cancer development, exosomes have become a focus of the search for a new therapeutic method for cancer. Exosomes can be utilized for the therapeutic delivery of small molecules, proteins and RNAs to target cancer cells with a high efficiency. Exosome-carried proteins, lipids and nucleic acids are being tested as promising biomarkers for cancer diagnosis and prognosis, even as potential treatment targets for cancer. Moreover, different sources of exosomes exhibit multiple performances in cancer applications. In this review, we elaborate on the specific mechanism by which exosomes affect the communication between tumors and the microenvironment and state the therapeutic and diagnostic applications of exosomes in cancers.

Siqi Luo

Papers

The Role of Exosomes and Their Applications in Cancer