Clinical Applications of Circulating Tumor DNA, Circulating Tumor Cells, and Exosomes as Liquid Biopsy-Based Tumor Biomarkers

Xiaoshuang Yan, Chao-Chi Yeh, Linglong Zou
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Abstract

Along with improved knowledge of cancer biology and biotechnical progress, the diagnostic approaches have evolved from tissue biopsies to liquid biopsies. As they provide a minimally invasive tumor detection, liquid biopsies allow early diagnosis and serial assessments of tumor progression. Discovery and use of circulating tumor markers circulating tumor DNA (ctDNA), circulating tumor cells (CTC), and exosomes have largely expanded the possibility of early diagnosis of cancer, patient stratification, as well as developing a personalized treatment. Based on these circulomes, liquid biopsies can be developed, but each type of liquid biopsies has its own merits and limitations. While ctDNA-based methods represent the most advanced techniques, sensitivity improvement is expected given the rarity of ctDNA in circulation. As intact cancer cells, CTC provide information on cancer cells. However, current CTC capturing procedures are still lack of efficiency. Exosomes are abundant, but they are highly heterogeneous and there is a lack of specific markers for identification. Future efforts are needed to improve operational parameters and clinical performance of each method. Prior to a broad use in clinical settings, it is crucial to standardize the procedure for the specific liquid biopsy method and validate the test with adequate specificity and sensitivity for clinical applications.
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循环肿瘤DNA、循环肿瘤细胞和外泌体作为液体活检肿瘤生物标志物的临床应用
随着癌症生物学知识的提高和生物技术的进步,诊断方法已经从组织活检发展到液体活检。由于液体活检提供了一种微创肿瘤检测,因此可以对肿瘤进展进行早期诊断和系列评估。循环肿瘤标志物循环肿瘤DNA (ctDNA)、循环肿瘤细胞(CTC)和外泌体的发现和使用极大地扩展了癌症早期诊断、患者分层以及开发个性化治疗的可能性。基于这些循环,液体活检可以发展,但每种类型的液体活检都有其自身的优点和局限性。虽然基于ctDNA的方法代表了最先进的技术,但考虑到循环中ctDNA的稀有性,灵敏度有望提高。作为完整的癌细胞,CTC提供了有关癌细胞的信息。然而,目前的CTC捕获程序仍然缺乏效率。外泌体是丰富的,但它们是高度异质的,缺乏特异性的标记物进行鉴定。每种方法的操作参数和临床表现有待进一步改进。在临床广泛应用之前,对特定液体活检方法的程序进行标准化,并对临床应用具有足够的特异性和敏感性进行验证是至关重要的。
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