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循环肿瘤DNA(ctDNA)在评估免疫治疗疗效方面具有广阔的临床应用前景。

Promising clinical application of ctDNA in evaluating immunotherapy efficacy.

作者信息

Li Li, Zhang Jun, Jiang Xiaoyue, Li Qin

机构信息

Department of Oncology, Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.

Department of Hematopathology, University of Texas MD Anderson Cancer Center Houston, TX 77030, US.

出版信息

Am J Cancer Res. 2018 Oct 1;8(10):1947-1956. eCollection 2018.

PMID:30416847
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6220137/
Abstract

An increasing number of promising immunotherapies and related clinical trials have led to several major breakthroughs in multiple cancers, but a reliable and precise biomarker for evaluating efficacy and prognosis has not yet been established. As a typical representation of a liquid biopsy, circulating cell-free DNA (ctDNA) possesses the functions and advantages of tissue biopsy but its distinct advantages of convenience, real-time nature, non-invasiveness and homogeneity make it superior to tissue biopsy. Indeed, compared with routine imaging and tumor markers, ctDNA offers an earlier indication and provides more precise information. ctDNA is reportedly able to identify immunotherapy responders, evaluate efficacy and survival time, screen immune checkpoint inhibitor resistance and pseudo-progress and predict tumor recurrence and metastasis. Thus, ctDNA can act as an "Eagle Eye" by comprehensively monitoring both macro- and micro-changes in the immunotherapy process. Although ctDNA has become a research topic of interest, its limitations cannot be ignored, and improvements in its sensitivity and standardization are urgently needed. This review reveals the advantages and limitations of ctDNA as a precise biomarker and supports the feasibility of using ctDNA detection for common monitoring during immunotherapy.

摘要

越来越多有前景的免疫疗法及相关临床试验已在多种癌症领域取得了多项重大突破,但尚未建立用于评估疗效和预后的可靠且精确的生物标志物。作为液体活检的典型代表,循环游离DNA(ctDNA)具备组织活检的功能和优势,但其便利性、实时性、非侵入性和均一性等独特优势使其优于组织活检。事实上,与常规影像学检查和肿瘤标志物相比,ctDNA能更早地给出指示并提供更精确的信息。据报道,ctDNA能够识别免疫治疗的反应者、评估疗效和生存时间、筛查免疫检查点抑制剂耐药性和假性进展,并预测肿瘤复发和转移。因此,ctDNA可通过全面监测免疫治疗过程中的宏观和微观变化,充当一只“鹰眼”。尽管ctDNA已成为一个备受关注的研究课题,但其局限性不容忽视,迫切需要提高其灵敏度和标准化水平。本综述揭示了ctDNA作为精确生物标志物的优势和局限性,并支持在免疫治疗期间使用ctDNA检测进行常规监测的可行性。

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本文引用的文献

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Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA.通过循环肿瘤 DNA 早期评估肺癌免疫治疗反应。
Clin Cancer Res. 2018 Apr 15;24(8):1872-1880. doi: 10.1158/1078-0432.CCR-17-1341. Epub 2018 Jan 12.
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Tumor Mutational Burden and Response Rate to PD-1 Inhibition.肿瘤突变负荷与对PD-1抑制的反应率
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Detection of mutations in circulating tumor DNA from patients with ovarian cancer.卵巢癌患者循环肿瘤DNA中突变的检测。
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Circulating Tumor DNA Reveals Clinically Actionable Somatic Genome of Metastatic Bladder Cancer.循环肿瘤 DNA 揭示转移性膀胱癌的临床可操作体细胞基因组。
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Circulating tumour DNA (ctDNA) as a liquid biopsy for melanoma.循环肿瘤DNA(ctDNA)作为黑色素瘤的液体活检
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HPV circulating tumor DNA to monitor the efficacy of anti-PD-1 therapy in metastatic squamous cell carcinoma of the anal canal: A case report.HPV 循环肿瘤 DNA 监测抗 PD-1 治疗转移性肛门鳞癌的疗效:一例报告。
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Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study.循环肿瘤 DNA 变化用于抗 PD-1 免疫治疗的早期监测:一项概念验证研究。
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