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文献精选 > 高引权威"液体活检"文献

Integrating liquid biopsies into the management of cancer. ​

文献信息 ​

DOI10.1038/nrclinonc.2017.14
PMID28252003
期刊Nature reviews. Clinical oncology
影响因子82.2
JCR 分区Q1
发表年份2017
被引次数906
关键词液体活检, 循环肿瘤DNA, 肿瘤异质性, 药物耐受性, 临床肿瘤学
文献类型Journal Article, Review
ISSN1759-4774
页码531-548
期号14(9)
作者Giulia Siravegna, Silvia Marsoni, Salvatore Siena, Alberto Bardelli

一句话小结 ​

本研究探讨了利用循环肿瘤游离DNA（ctDNA）进行液体活检，以克服传统组织样本在肿瘤异质性评估中的局限性，发现ctDNA的基因组特征与肿瘤特征高度匹配，具有监测治疗反应和评估耐药性的重要意义。通过整合不同体液中的肿瘤来源遗传信息，液体活检有望在临床实践中为患者提供更精准的护理指导。

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液体活检 · 循环肿瘤DNA · 肿瘤异质性 · 药物耐受性 · 临床肿瘤学

摘要 ​

在癌症进展和治疗过程中，多种亚克隆肿瘤细胞相互竞争，选择性压力导致了主要亚克隆的出现，这些亚克隆具有最强的增殖和传播能力，并且对治疗的敏感性最低。目前，实体肿瘤的分子特征是通过手术或活检组织样本建立的。然而，基于组织的肿瘤特征容易受到取样偏倚的影响，仅能提供肿瘤异质性的快照，并且无法反复获取。循环肿瘤游离DNA（ctDNA）的基因组特征已被证明与相应肿瘤的特征密切匹配，这对分子病理学和临床肿瘤学具有重要意义。循环核酸的分析，通常称为“液体活检”，可用于监测治疗反应、评估耐药性的出现以及量化微小残留疾病。除了血液外，其他一些体液，如尿液、唾液、胸腔积液和脑脊液，也可以包含肿瘤来源的遗传信息。从ctDNA收集的分子特征可以通过对循环肿瘤细胞（CTCs）以及存在于小泡（如外泌体）中的RNA、蛋白质和脂质的分析进一步补充。在本综述中，我们探讨了如何利用不同形式的液体活检来指导患者护理，并最终应将其整合到临床实践中，重点关注ctDNA的液体活检——无疑是目前临床上最先进的方法。

英文摘要 ​

During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly. Genomic profiles of circulating cell-free tumour DNA (ctDNA) have been shown to closely match those of the corresponding tumours, with important implications for both molecular pathology and clinical oncology. Analyses of circulating nucleic acids, commonly referred to as 'liquid biopsies', can be used to monitor response to treatment, assess the emergence of drug resistance, and quantify minimal residual disease. In addition to blood, several other body fluids, such as urine, saliva, pleural effusions, and cerebrospinal fluid, can contain tumour-derived genetic information. The molecular profiles gathered from ctDNA can be further complemented with those obtained through analysis of circulating tumour cells (CTCs), as well as RNA, proteins, and lipids contained within vesicles, such as exosomes. In this Review, we examine how different forms of liquid biopsies can be exploited to guide patient care and should ultimately be integrated into clinical practice, focusing on liquid biopsy of ctDNA - arguably the most clinically advanced approach.

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主要研究问题 ​

  1. 在不同类型的癌症中，液体活检的应用效果有何差异？
  2. 如何评估液体活检在监测癌症治疗反应中的准确性和可靠性？
  3. 液体活检在早期癌症筛查中的潜力如何，与传统组织活检相比有什么优势？
  4. 在液体活检中，如何结合ctDNA与循环肿瘤细胞（CTCs）的分析以提高临床决策的有效性？
  5. 液体活检在个体化治疗方案制定中的作用是什么，是否能够改善患者的预后？

核心洞察 ​

1. 研究背景和目的 ​

在癌症的进展和治疗过程中，肿瘤细胞的多种亚克隆群体之间存在竞争关系。这种竞争受到选择压力的影响，最终导致一些主要亚克隆的出现，它们在繁殖和传播方面更为有效，并且对治疗的抗性更强。目前，固体肿瘤的分子特征通常依赖于外科手术或活检样本的分析。然而，组织样本容易受到取样偏差的影响，只能提供肿瘤异质性的快照，且无法频繁获取。因此，本研究旨在探讨将液体活检（尤其是循环肿瘤DNA，ctDNA）整合到癌症管理中的潜力，以期改善患者的个体化治疗和监测。

2. 主要方法和发现 ​

研究分析了液体活检的不同形式，包括ctDNA、循环肿瘤细胞（CTCs）以及包含在外泌体等囊泡中的RNA、蛋白质和脂质。ctDNA的基因组特征被发现与相应肿瘤的分子特征高度匹配，表明其在分子病理学和临床肿瘤学中的重要性。液体活检能够实时监测患者对治疗的反应、评估药物抗性的发展，并定量分析微小残留病（MRD）。此外，研究还指出，除了血液，尿液、唾液、胸腔积液和脑脊液等其他体液也可以提供肿瘤来源的遗传信息。

3. 核心结论 ​

液体活检，尤其是ctDNA的分析，具有重要的临床应用潜力。通过对液体活检的应用，可以更好地指导癌症患者的治疗决策，监测疾病进展及治疗效果，评估治疗耐药性，并实现对微小残留病的早期发现。这种方法为癌症管理提供了一个动态和全面的视角，超越了传统的组织活检限制。

4. 研究意义和影响 ​

将液体活检整合到癌症管理中，能够显著提高患者的个体化治疗水平，减少对传统组织样本的依赖, 并改善肿瘤监测的灵活性和准确性。这项研究强调了液体活检在癌症诊疗中的重要性，可能引领未来的临床实践变革，为癌症患者提供更为精准和及时的治疗方案，从而提高整体治疗效果和生存率。

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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. What We Know About Stage II and III Colon Cancer: It's Still Not Enough. - Alberto Puccini;Martin D Berger;Wu Zhang;Heinz-Josef Lenz - Targeted oncology (2017)
  3. Early phase clinical trials of anticancer agents in children and adolescents - an ITCC perspective. - Lucas Moreno;Andrew D J Pearson;Xavier Paoletti;Irene Jimenez;Birgit Geoerger;Pamela R Kearns;C Michel Zwaan;Francois Doz;Andre Baruchel;Josef Vormoor;Michela Casanova;Stefan M Pfister;Bruce Morland;Gilles Vassal; - Nature reviews. Clinical oncology (2017)
  4. Salivary exosomal PSMA7: a promising biomarker of inflammatory bowel disease. - Xiaowen Zheng;Feng Chen;Qian Zhang;Yulan Liu;Peng You;Shan Sun;Jiuxiang Lin;Ning Chen - Protein & cell (2017)
  5. Medical research: Personalized test tracks cancer relapse. - Alberto Bardelli - Nature (2017)
  6. Changes of Microrna Levels in Plasma of Patients with Rectal Cancer during Chemoradiotherapy. - Peter Jo;Azadeh Azizian;Junius Salendo;Frank Kramer;Markus Bernhardt;Hendrik A Wolff;Jens Gruber;Marian Grade;Tim Beißbarth;B Michael Ghadimi;Jochen Gaedcke - International journal of molecular sciences (2017)
  7. Extracellular Vesicles in Hematological Malignancies: From Biology to Therapy. - Antonella Caivano;Francesco La Rocca;Ilaria Laurenzana;Stefania Trino;Luciana De Luca;Daniela Lamorte;Luigi Del Vecchio;Pellegrino Musto - International journal of molecular sciences (2017)
  8. Optofluidic device for the quantification of circulating tumor cells in breast cancer. - Eric Pedrol;Manuel Garcia-Algar;Jaume Massons;Moritz Nazarenus;Luca Guerrini;Javier Martínez;Airan Rodenas;Ana Fernandez-Carrascal;Magdalena Aguiló;Laura G Estevez;Isabel Calvo;Ana Olano-Daza;Eduardo Garcia-Rico;Francesc Díaz;Ramon A Alvarez-Puebla - Scientific reports (2017)
  9. Prostate Cancer Stem Cell Markers Drive Progression, Therapeutic Resistance, and Bone Metastasis. - Koran S Harris;Bethany A Kerr - Stem cells international (2017)
  10. The past and future of breast cancer treatment-from the papyrus to individualised treatment approaches. - Felipe Ades;Konstantinos Tryfonidis;Dimitrios Zardavas - Ecancermedicalscience (2017)

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