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Liquid biopsies come of age: towards implementation of circulating tumour DNA. ​

文献信息 ​

DOI10.1038/nrc.2017.7
PMID28233803
期刊Nature reviews. Cancer
影响因子66.8
JCR 分区Q1
发表年份2017
被引次数1218
关键词循环肿瘤DNA, 液体活检, 个性化肿瘤学
文献类型Journal Article, Review
ISSN1474-175X
页码223-238
期号17(4)
作者Jonathan C M Wan, Charles Massie, Javier Garcia-Corbacho, Florent Mouliere, James D Brenton, Carlos Caldas, Simon Pacey, Richard Baird, Nitzan Rosenfeld

一句话小结 ​

随着基因组和分子技术的进步，循环肿瘤DNA（ctDNA）的应用正逐步扩展至癌症管理中的液体活检，并在预后评估和监测中展现出转化潜力。尽管对无细胞DNA的生物学仍需深入研究，但ctDNA分析为个性化肿瘤学和癌症研究提供了新的机遇。

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循环肿瘤DNA · 液体活检 · 个性化肿瘤学

摘要 ​

基因组和分子方法的改进正在拓展循环肿瘤DNA（ctDNA）的潜在应用范围，包括在研究环境中以及作为癌症管理的“液体活检”。原理验证研究已经证明了ctDNA在预后评估、分子特征分析和监测方面的转化潜力。该领域目前正处于一个激动人心的过渡期，ctDNA分析开始在临床上得到应用，尽管我们对无细胞DNA的生物学仍有很多需要学习的地方。这是一个审视ctDNA分析潜在方法的良机，同时考虑其在个性化肿瘤学和癌症研究中的应用。

英文摘要 ​

Improvements in genomic and molecular methods are expanding the range of potential applications for circulating tumour DNA (ctDNA), both in a research setting and as a 'liquid biopsy' for cancer management. Proof-of-principle studies have demonstrated the translational potential of ctDNA for prognostication, molecular profiling and monitoring. The field is now in an exciting transitional period in which ctDNA analysis is beginning to be applied clinically, although there is still much to learn about the biology of cell-free DNA. This is an opportune time to appraise potential approaches to ctDNA analysis, and to consider their applications in personalized oncology and in cancer research.

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主要研究问题 ​

  1. 在液体活检的临床应用中，ctDNA的检测方法与传统组织活检相比有哪些优势和劣势？
  2. ctDNA分析在个性化肿瘤治疗中的具体应用案例有哪些，能否分享一些成功的临床研究结果？
  3. 当前在ctDNA研究中存在哪些技术挑战和生物学理解的盲点，未来的研究方向可能是什么？
  4. 如何评估ctDNA在不同类型癌症中的预后价值，是否存在特定的生物标志物可以用于不同癌症的监测？
  5. 在液体活检的推广过程中，患者对ctDNA测试的接受度和理解程度如何影响其临床应用？

核心洞察 ​

研究背景和目的 ​

液体活检（Liquid biopsy）是一种新兴的非侵入性技术，通过分析循环肿瘤DNA（ctDNA）来监测癌症的发生、发展和治疗反应。随着基因组学和分子生物学方法的进步，ctDNA在癌症管理中的应用逐渐增多。本研究旨在评估ctDNA分析的潜在方法及其在个性化肿瘤学和癌症研究中的应用。

主要方法/材料/实验设计 ​

本研究采用文献综述的方法，回顾了ctDNA的生物学特性、检测技术及其在临床中的应用。主要技术路线包括：

Mermaid diagram

关键结果和发现 ​

  1. ctDNA的生物学特性：ctDNA主要来源于肿瘤细胞的凋亡和坏死，且其片段长度通常较短，约为134-144 bp。
  2. 检测技术：使用数字PCR（dPCR）、高通量测序等技术可以高灵敏度地检测ctDNA，能够实现对癌症的早期诊断和动态监测。
  3. 临床应用：ctDNA在癌症检测、预后评估、治疗监测及个性化治疗中展现出良好的前景，尤其在监测治疗反应和识别残留疾病方面表现突出。

主要结论/意义/创新性 ​

ctDNA分析为癌症的非侵入性监测提供了新方法，具有高灵敏度和特异性。其应用可以实现早期诊断、个性化治疗选择及实时监测肿瘤动态变化，推动癌症管理向个性化和精准化发展。

研究局限性和未来方向 ​

尽管ctDNA在癌症监测中展现出广阔前景，但仍存在以下局限性：

  • 生物学因素：ctDNA的释放和清除机制尚不完全明确，可能影响检测结果的可靠性。
  • 技术挑战：现有技术在检测低丰度ctDNA时仍面临灵敏度不足的问题。 未来的研究应着重于以下几个方向：
  • 加强对ctDNA生物学特性的研究，以改善其临床应用。
  • 开发更高灵敏度的检测技术，以提高早期癌症检测的准确性。
  • 探索ctDNA与其他生物标志物的联合应用，进一步提高癌症管理的有效性。

参考文献 ​

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引用本文的文献 ​

  1. Implementing liquid biopsies into clinical decision making for cancer immunotherapy. - Dagmar Quandt;Hans Dieter Zucht;Arno Amann;Anne Wulf-Goldenberg;Carl Borrebaeck;Michael Cannarile;Diether Lambrechts;Herbert Oberacher;James Garrett;Tapan Nayak;Michael Kazinski;Charles Massie;Heidi Schwarzenbach;Michele Maio;Robert Prins;Björn Wendik;Richard Hockett;Daniel Enderle;Mikkel Noerholm;Hans Hendriks;Heinz Zwierzina;Barbara Seliger - Oncotarget (2017)
  2. Medical research: Personalized test tracks cancer relapse. - Alberto Bardelli - Nature (2017)
  3. CVE: an R package for interactive variant prioritisation in precision oncology. - Andreas Mock;Suzanne Murphy;James Morris;Francesco Marass;Nitzan Rosenfeld;Charlie Massie - BMC medical genomics (2017)
  4. Comparative analysis of 12 different kits for bisulfite conversion of circulating cell-free DNA. - Mai-Britt Worm Ørntoft;Sarah Østrup Jensen;Thomas Birkballe Hansen;Jesper Bertram Bramsen;Claus Lindbjerg Andersen - Epigenetics (2017)
  5. Predicting lung cancer recurrence from circulating tumour DNA. Commentary on 'Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution'. - Daniel J Murphy;Kevin G Blyth - Cell death and differentiation (2017)
  6. Circulating tumor DNA: Solid data from liquid biopsies. - David S Schrump - The Journal of thoracic and cardiovascular surgery (2017)
  7. Correlation between circulating mutant DNA and metabolic tumour burden in advanced non-small cell lung cancer patients. - Anne Winther-Larsen;Christina Demuth;Joan Fledelius;Anne Tranberg Madsen;Karin Hjorthaug;Peter Meldgaard;Boe Sandahl Sorensen - British journal of cancer (2017)
  8. Personalized medicine could transform healthcare. - Sunil Mathur;Joseph Sutton - Biomedical reports (2017)
  9. Endoscopic Management of Early Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus: Screening, Diagnosis, and Therapy. - Massimiliano di Pietro;Marcia I Canto;Rebecca C Fitzgerald - Gastroenterology (2018)
  10. Detection of urine DNA markers for monitoring recurrent hepatocellular carcinoma. - Hie-Won Hann;Surbhi Jain;Grace Park;Jamin D Steffen;Wei Song;Ying-Hsiu Su - Hepatoma research (2017)

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