Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Department of Pathology, McGill University, Montreal, QC, Canada.
Cell Death Dis. 2024 Sep 12;15(9):668. doi: 10.1038/s41419-024-07003-y.
Extracellular vesicles (EVs) have emerged as key players in intercellular communication, facilitating the transfer of crucial cargo between cells. Liquid biopsy, particularly through the isolation of EVs, has unveiled a rich source of potential biomarkers for health and disease, encompassing proteins and nucleic acids. A milestone in this exploration occurred a decade ago with the identification of extracellular vesicle-associated DNA (EV-DNA) in the bloodstream of a patient diagnosed with pancreatic cancer. Subsequent years have witnessed substantial advancements, deepening our insights into the molecular intricacies of EV-DNA emission, detection, and analysis. Understanding the complexities surrounding the release of EV-DNA and addressing the challenges inherent in EV-DNA research are pivotal steps toward enhancing liquid biopsy-based strategies. These strategies, crucial for the detection and monitoring of various pathological conditions, particularly cancer, rely on a comprehensive understanding of why and how EV-DNA is released. In our review, we aim to provide a thorough summary of a decade's worth of research on EV-DNA. We will delve into diverse mechanisms of EV-DNA emission, its potential as a biomarker, its functional capabilities, discordant findings in the field, and the hurdles hindering its clinical application. Looking ahead to the next decade, we envision that advancements in EV isolation and detection techniques, coupled with improved standardization and data sharing, will catalyze the development of novel strategies exploiting EV-DNA as both a source of biomarkers and therapeutic targets.
细胞外囊泡 (EVs) 已成为细胞间通讯的关键参与者，促进了细胞间关键物质的传递。液体活检，特别是通过 EV 的分离，揭示了丰富的健康和疾病潜在生物标志物来源，包括蛋白质和核酸。十年前，在诊断为胰腺癌的患者的血液中发现了细胞外囊泡相关 DNA (EV-DNA)，这是该探索领域的一个里程碑。此后的几年里，我们对 EV-DNA 释放的分子复杂性的认识有了实质性的进展，并加深了对其检测和分析的理解。了解 EV-DNA 释放的复杂性并解决 EV-DNA 研究中固有的挑战，是增强基于液体活检的策略的关键步骤。这些策略对于检测和监测各种病理状况（特别是癌症）至关重要，依赖于对 EV-DNA 为何以及如何释放的全面理解。在我们的综述中，我们旨在对 EV-DNA 十年的研究进行全面总结。我们将深入探讨 EV-DNA 释放的多种机制、其作为生物标志物的潜力、其功能能力、该领域的不一致发现以及阻碍其临床应用的障碍。展望未来十年，我们设想 EV 分离和检测技术的进步，以及标准化和数据共享的改善，将加速利用 EV-DNA 作为生物标志物和治疗靶点的新策略的发展。
