在临床试验中实施液体活检：现状、机遇与挑战。
Implementing Liquid Biopsies in Clinical Trials: State of Affairs, Opportunities, and Challenges.
作者信息
Lustberg Maryam B, Stover Daniel G, Chalmers Jeffrey J
出版信息
Cancer J. 2018 Mar/Apr;24(2):61-64. doi: 10.1097/PPO.0000000000000309.
Abstract
A primary goal of personalized medicine is to develop tumor-specific biomarkers to aid in treatment selection and to better evaluate response to targeted therapies. The assessment of circulating blood markers as surrogate real-time biopsies of disease status, termed liquid biopsies, has been under investigation. There are many different types of liquid biopsies each with different functionalities and limitations. These include tumor markers, circulating tumor cells, cell-free DNA, and extracellular vesicles including exosomes. Multiple clinical trials have evaluated liquid biopsies as prognostic biomarkers with positive results. Additional studies are underway to evaluate liquid biopsies as predictive biomarkers, pharmacodynamic biomarkers, and surrogate efficacy endpoints for treatment response evaluation. There are several challenges in and barriers to implementation of liquid biopsies into clinical trials and subsequently into routine clinical practice, which are addressed in this review.
摘要
精准医学的一个主要目标是开发肿瘤特异性生物标志物，以辅助治疗选择并更好地评估对靶向治疗的反应。将循环血液标志物评估作为疾病状态的替代实时活检，即所谓的液体活检，一直在研究中。有许多不同类型的液体活检，每种都有不同的功能和局限性。这些包括肿瘤标志物、循环肿瘤细胞、游离DNA以及包括外泌体在内的细胞外囊泡。多项临床试验已将液体活检评估为预后生物标志物，结果呈阳性。正在进行更多研究，以评估液体活检作为预测性生物标志物、药效学生物标志物以及用于治疗反应评估的替代疗效终点。将液体活检应用于临床试验并随后应用于常规临床实践存在若干挑战和障碍，本综述将对此进行探讨。
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本文引用的文献
1
Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small-cell lung cancer.检测晚期非小细胞肺癌患者循环肿瘤细胞和白细胞中的 PD-L1。
Ann Oncol. 2018 Jan 1;29(1):193-199. doi: 10.1093/annonc/mdx636.
2
Patient-Paired Sample Congruence Between 2 Commercial Liquid Biopsy Tests.患者配对样本在 2 种商业液体活检检测中的一致性。
JAMA Oncol. 2018 Jun 1;4(6):868-870. doi: 10.1001/jamaoncol.2017.4027.
3
Technical Advances to Study Extracellular Vesicles.用于研究细胞外囊泡的技术进展
Front Mol Biosci. 2017 Nov 28;4:79. doi: 10.3389/fmolb.2017.00079. eCollection 2017.
4
Extracellular vesicles compartment in liquid biopsies: Clinical application.液体活检中的细胞外囊泡室：临床应用。
Mol Aspects Med. 2018 Apr;60:27-37. doi: 10.1016/j.mam.2017.11.009. Epub 2017 Nov 26.
5
Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors.可扩展的游离细胞 DNA 全外显子组测序与转移性肿瘤具有高度一致性。
Nat Commun. 2017 Nov 6;8(1):1324. doi: 10.1038/s41467-017-00965-y.
6
Multispectral Imaging Analysis of Circulating Tumor Cells in Negatively Enriched Peripheral Blood Samples.阴性富集外周血样本中循环肿瘤细胞的多光谱成像分析
Methods Mol Biol. 2017;1634:219-234. doi: 10.1007/978-1-4939-7144-2_19.
7
Shallow Whole Genome Sequencing on Circulating Cell-Free DNA Allows Reliable Noninvasive Copy-Number Profiling in Neuroblastoma Patients.对循环游离 DNA 进行浅层全基因组测序可在神经母细胞瘤患者中实现可靠的非侵入性拷贝数分析。
Clin Cancer Res. 2017 Oct 15;23(20):6305-6314. doi: 10.1158/1078-0432.CCR-17-0675. Epub 2017 Jul 14.
8
Concordance of Genomic Alterations by Next-Generation Sequencing in Tumor Tissue versus Circulating Tumor DNA in Breast Cancer.下一代测序在乳腺癌肿瘤组织与循环肿瘤 DNA 中基因组改变的一致性。
Mol Cancer Ther. 2017 Jul;16(7):1412-1420. doi: 10.1158/1535-7163.MCT-17-0061. Epub 2017 Apr 26.
9
Multiparameter Evaluation of the Heterogeneity of Circulating Tumor Cells Using Integrated RNA Hybridization and Immunocytochemical Analysis.使用整合RNA杂交和免疫细胞化学分析对循环肿瘤细胞的异质性进行多参数评估。
Front Oncol. 2016 Nov 8;6:234. doi: 10.3389/fonc.2016.00234. eCollection 2016.
10
Programmed death-ligand 1 (PD-L1) characterization of circulating tumor cells (CTCs) in muscle invasive and metastatic bladder cancer patients.肌肉浸润性和转移性膀胱癌患者循环肿瘤细胞（CTC）的程序性死亡配体1（PD-L1）特征分析
BMC Cancer. 2016 Sep 22;16(1):744. doi: 10.1186/s12885-016-2758-3.
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