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基于外泌体的癌症液体活检:机遇与挑战。

Exosome-based liquid biopsies in cancer: opportunities and challenges.

机构信息

Exosome Diagnostics, Inc., a Bio-Techne brand, Waltham, USA.

Exosome Diagnostics GmbH, a Bio-Techne brand, Martinsried, Germany.

出版信息

Ann Oncol. 2021 Apr;32(4):466-477. doi: 10.1016/j.annonc.2021.01.074. Epub 2021 Feb 4.

Abstract

Liquid biopsy in cancer has gained momentum in clinical research and is experiencing a boom for a variety of applications. There are significant efforts to utilize liquid biopsies in cancer for early detection and treatment stratification, as well as residual disease and recurrence monitoring. Although most efforts have used circulating tumor cells and circulating tumor DNA for this purpose, exosomes and other extracellular vesicles have emerged as a platform with potentially broader and complementary applications. Exosomes/extracellular vesicles are small vesicles released by cells, including cancer cells, into the surrounding biofluids. These exosomes contain tumor-derived materials such as DNA, RNA, protein, lipid, sugar structures, and metabolites. In addition, exosomes carry molecules on their surface that provides clues regarding their origin, making it possible to sort vesicle types and enrich signatures from tissue-specific origins. Exosomes are part of the intercellular communication system and cancer cells frequently use them as biological messengers to benefit their growth. Since exosomes are part of the disease process, they have become of tremendous interest in biomarker research. Exosomes are remarkably stable in biofluids, such as plasma and urine, and can be isolated for clinical evaluation even in the early stages of the disease. Exosome-based biomarkers have quickly become adopted in the clinical arena and the first exosome RNA-based prostate cancer test has already helped >50 000 patients in their decision process and is now included in the National Comprehensive Cancer Network guidelines for early prostate cancer detection. This review will discuss the advantages and challenges of exosome-based liquid biopsies for tumor biomarkers and clinical implementation in the context of circulating tumor DNA and circulating tumor cells.

摘要

液体活检在癌症领域的临床研究中得到了迅猛发展,在各种应用中呈现出蓬勃发展的态势。人们正在积极努力地将液体活检应用于癌症的早期检测和治疗分层,以及残留疾病和复发监测。尽管大多数研究都将循环肿瘤细胞和循环肿瘤 DNA 用于这一目的,但外泌体和其他细胞外囊泡已成为一种具有潜在更广泛和互补应用的平台。外泌体/细胞外囊泡是细胞(包括癌细胞)释放到周围生物体液中的小囊泡。这些外泌体包含源自肿瘤的物质,如 DNA、RNA、蛋白质、脂质、糖结构和代谢物。此外,外泌体表面携带的分子提供了关于其起源的线索,从而可以对囊泡类型进行分类,并从组织特异性起源中富集特征。外泌体是细胞间通讯系统的一部分,癌细胞经常将其用作生物信使,以促进自身生长。由于外泌体是疾病过程的一部分,因此它们在生物标志物研究中引起了极大的关注。外泌体在生物体液(如血浆和尿液)中非常稳定,即使在疾病早期也可以进行分离用于临床评估。基于外泌体的生物标志物已迅速在临床领域得到采用,第一个基于外泌体 RNA 的前列腺癌检测已经帮助了 >50000 名患者做出决策,现在已被纳入国家综合癌症网络早期前列腺癌检测指南。本文将讨论基于外泌体的液体活检在循环肿瘤 DNA 和循环肿瘤细胞背景下作为肿瘤生物标志物的优势和挑战,以及其临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6cf/8268076/029c2b3fac12/nihms-1720092-f0001.jpg

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