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文献精选 > 近年高分"液体活检"研究（IF≥30，近5年）

The functional and clinical roles of liquid biopsy in patient-derived models. ​

文献信息 ​

DOI10.1186/s13045-023-01433-5
PMID37031172
期刊Journal of hematology & oncology
影响因子40.4
JCR 分区Q1
发表年份2023
被引次数24
关键词液体活检, 患者源性类器官, 患者源性异种移植
文献类型Journal Article, Review, Research Support, Non-U.S. Gov't
ISSN1756-8722
页码36
期号16(1)
作者Ziqing Zhu, Erya Hu, Hong Shen, Jun Tan, Shan Zeng

一句话小结 ​

本综述探讨了液体活检在癌症研究中的应用，重点介绍了患者源异种移植（PDX）、CTC源异种移植（CDX）和患者源类器官（PDO）如何通过新技术推动循环肿瘤细胞及其相关生物标志物的研究，促进早期诊断和治疗反应监测。研究表明，这些患者源模型在揭示肿瘤特性和药物反应方面具有重要潜力，尽管仍面临诸多挑战。

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液体活检 · 患者源性类器官 · 患者源性异种移植

摘要 ​

液体活检包括在血液中检测循环肿瘤细胞（CTCs）及CTC簇，以及在患者体液中检测游离DNA（cfDNA）/循环肿瘤DNA（ctDNA）和细胞外囊泡（EVs）。液体活检在转化研究中具有重要作用，但其临床应用仍在研究中。新近出现的患者源异种移植（PDX）和CTC源异种移植（CDX）忠实地再现了供体患者肿瘤的遗传和形态特征，而患者源类器官（PDO）则在很大程度上可以模拟肿瘤生长、肿瘤微环境及其对药物的反应。在本综述中，我们描述了这些患者源模型的发展如何通过最新技术辅助CTCs和CTC簇的研究，包括肿瘤生物行为探索、基因组分析和药物测试。接着，我们总结了在PDX和PDO模型中关于EVs和cfDNA/ctDNA的研究，这些研究涉及早期癌症诊断、肿瘤负担监测、药物测试与反应监测以及分子特征分析。我们还讨论了使用患者源模型进行液体活检研究所面临的挑战和未来展望。

英文摘要 ​

The liquid biopsy includes the detection of circulating tumor cells (CTCs) and CTC clusters in blood, as well as the detection of, cell-free DNA (cfDNA)/circulating tumor DNA (ctDNA) and extracellular vesicles (EVs) in the patient's body fluid. Liquid biopsy has important roles in translational research. But its clinical utility is still under investigation. Newly emerged patient-derived xenograft (PDX) and CTC-derived xenograft (CDX) faithfully recapitulate the genetic and morphological features of the donor patients' tumor and patient-derived organoid (PDO) can mostly mimic tumor growth, tumor microenvironment and its response to drugs. In this review, we describe how the development of these patient-derived models has assisted the studies of CTCs and CTC clusters in terms of tumor biological behavior exploration, genomic analysis, and drug testing, with the help of the latest technology. We then summarize the studies of EVs and cfDNA/ctDNA in PDX and PDO models in early cancer diagnosis, tumor burden monitoring, drug test and response monitoring, and molecular profiling. The challenges faced and future perspectives of research related to liquid biopsy using patient-derived models are also discussed.

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主要研究问题 ​

  1. 在液体活检中，如何评估循环肿瘤细胞（CTCs）和细胞游离DNA（cfDNA）的临床应用价值？
  2. 患者衍生模型（如PDX和PDO）如何在液体活检的研究中推动新疗法的开发？
  3. 目前液体活检技术在早期癌症诊断中的应用有哪些具体案例或成功实例？
  4. 液体活检在监测肿瘤负担和药物反应方面的优势与局限性是什么？
  5. 未来液体活检研究中，如何克服当前面临的挑战以提高其临床实用性？

核心洞察 ​

研究背景和目的 ​

液体活检技术在癌症管理中逐渐受到重视，因其获取方式相对简单、可重复性高且侵入性小。液体活检主要包括循环肿瘤细胞（CTCs）、游离DNA（cfDNA/ctDNA）和细胞外囊泡（EVs）的检测。尽管液体活检在转化研究中具有重要作用，但其临床应用仍在探索中。本文旨在探讨患者来源模型（如患者来源异种移植模型PDX、CTC衍生异种移植模型CDX和患者来源类器官PDO）在液体活检研究中的功能和临床作用。

主要方法/材料/实验设计 ​

本研究综述了液体活检的不同成分在PDX、CDX和PDO模型中的应用。具体方法如下：

Mermaid diagram
  1. CTCs研究：通过PDX和CDX模型分析CTCs的生物学行为和基因组特征。
  2. cfDNA/ctDNA研究：在PDX和PDO模型中进行早期癌症诊断和药物反应监测。
  3. EVs研究：分析EVs在肿瘤微环境中的作用及其作为生物标志物的潜力。

关键结果和发现 ​

  1. CTCs的角色：CTCs不仅是肿瘤转移的先导，还可用于预后评估和治疗个性化。研究发现，CTCs与肿瘤负担密切相关，且CTC集群显示出更高的转移潜力。
  2. cfDNA/ctDNA的应用：cfDNA/ctDNA的分析能够监测肿瘤负担，并与临床治疗反应相关联。研究表明，ctDNA水平能够反映肿瘤体积变化。
  3. EVs的潜力：EVs作为生物标志物显示出在癌症发生、进展和预后监测中的应用潜力。

主要结论/意义/创新性 ​

本综述强调了患者来源模型在液体活检研究中的重要性，尤其是CDX模型在药物测试和个性化治疗中的应用。通过这些模型，研究者能够更好地理解肿瘤生物学，并为临床应用提供支持。患者来源模型的结合使用将为液体活检的临床转化提供新的思路和方向。

研究局限性和未来方向 ​

尽管患者来源模型在液体活检研究中显示出良好的应用前景，但仍存在一些局限性，如模型的建立和维护成本较高，且不同模型之间的生物学差异可能影响研究结果。未来的研究应集中在优化模型建立流程、提升模型的代表性以及探索新的生物标志物，以推动液体活检在临床中的应用。

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引用本文的文献 ​

  1. The role of organoids in cancer research. - Zhen Fang;Peijuan Li;Fengying Du;Liang Shang;Leping Li - Experimental hematology & oncology (2023)
  2. Beyond Extracellular Vesicles: Hybrid Membrane Nanovesicles as Emerging Advanced Tools for Biomedical Applications. - Meng Sun;Jiani Yang;Yueyun Fan;Yinfeng Zhang;Jian Sun;Min Hu;Ke Sun;Jinfeng Zhang - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
  3. Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy. - Matin Chehelgerdi;Fereshteh Behdarvand Dehkordi;Mohammad Chehelgerdi;Hamidreza Kabiri;Hosein Salehian-Dehkordi;Mohammad Abdolvand;Sharareh Salmanizadeh;Mohsen Rashidi;Anoosha Niazmand;Saba Ahmadi;Sara Feizbakhshan;Saber Kabiri;Nasimeh Vatandoost;Tayebeh Ranjbarnejad - Molecular cancer (2023)
  4. The role of extracellular vesicles in circulating tumor cell-mediated distant metastasis. - Siyin Guo;Jing Huang;Genpeng Li;Wenjie Chen;Zhihui Li;Jianyong Lei - Molecular cancer (2023)
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