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文献精选 > 近年高分"类器官"研究（IF≥30，近5年）

Organoid models of gastrointestinal cancers in basic and translational research. ​

文献信息 ​

DOI10.1038/s41575-019-0255-2
PMID32099092
期刊Nature reviews. Gastroenterology & hepatology
影响因子51.0
JCR 分区Q1
发表年份2020
被引次数96
关键词类器官技术, 胃肠癌, 肿瘤模型, 个性化医疗, 治疗反应
文献类型Journal Article, Review
ISSN1759-5045
页码203-222
期号17(4)
作者Harry Cheuk Hay Lau, Onno Kranenburg, Haipeng Xiao, Jun Yu

一句话小结 ​

本文回顾了类器官技术在胃肠道癌症研究中的应用，指出其在模拟肿瘤发生、转移以及预测患者治疗反应方面的重要价值，尤其相较于传统细胞培养方法能够更好地反映肿瘤的遗传和表型特征。研究表明，改进类器官模型有助于推动基础与转化研究，特别是在药物发现和个性化医学领域的发展。

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类器官技术 · 胃肠癌 · 肿瘤模型 · 个性化医疗 · 治疗反应

摘要 ​

癌症是全球范围内一个重大的公共健康问题。胃肠道癌症约占全球癌症发病率和死亡率的三分之一。历史上，胃肠道肿瘤的发生和进展机制主要通过体外癌细胞系和动物模型进行研究。传统的细胞培养方法往往会选择出强烈的基因组变异，这些变异不再反映原始肿瘤在（转移）行为或治疗反应方面的特征。类器官技术作为一种强有力的替代方法，已被提出用于培养胃肠道肿瘤及其相应的正常组织，从而保留其遗传、表型和行为特征。重要的是，越来越多的证据表明，类器官培养在预测个体患者的治疗结果方面具有重要价值。在本文中，我们回顾了当前关于最常见的胃肠道癌症（包括结直肠癌、胃癌、食管癌、肝癌和胰腺癌）类器官模型的文献，以及它们在模拟肿瘤发生、转移进展和治疗反应中的价值。我们还探讨了当前类器官模型的局限性，并讨论了如何改进这些模型，以便在未来最大程度地促进基础研究和转化研究，特别是在药物发现和个性化医学领域。

英文摘要 ​

Cancer is a major public health problem worldwide. Gastrointestinal cancers account for approximately one-third of the total global cancer incidence and mortality. Historically, the mechanisms of tumour initiation and progression in the gastrointestinal tract have been studied using cancer cell lines in vitro and animal models. Traditional cell culture methods are associated with a strong selection of aberrant genomic variants that no longer reflect the original tumours in terms of their (metastatic) behaviour or response to therapy. Organoid technology has emerged as a powerful alternative method for culturing gastrointestinal tumours and the corresponding normal tissues in a manner that preserves their genetic, phenotypic and behavioural traits. Importantly, accumulating evidence suggests that organoid cultures have great value in predicting the outcome of therapy in individual patients. Herein, we review the current literature on organoid models of the most common gastrointestinal cancers, including colorectal cancer, gastric cancer, oesophageal cancer, liver cancer and pancreatic cancer, and their value in modelling tumour initiation, metastatic progression and therapy response. We also explore the limitations of current organoid models and discuss how they could be improved to maximally benefit basic and translational research in the future, especially in the fields of drug discovery and personalized medicine.

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主要研究问题 ​

  1. 在肠道癌症的类器官模型中，如何确保其遗传特征和表型特征的准确性与原始肿瘤一致？
  2. 类器官技术在预测个体患者治疗结果方面的机制是什么？是否有具体的案例研究支持这一点？
  3. 与传统细胞培养方法相比，类器官模型在模拟肿瘤转移和药物反应方面的优势和局限性有哪些？
  4. 未来类器官模型在个性化医学和药物发现中的潜在应用场景有哪些？是否有新兴的研究方向？
  5. 当前类器官模型的改进方向是什么？在技术上有哪些创新可能提高其在基础和转化研究中的应用价值？

核心洞察 ​

1. 研究背景和目的 ​

肿瘤是全球范围内一个重大的公共卫生问题，而胃肠道癌症占全球癌症发病率和死亡率的约三分之一。传统上，胃肠道癌症的肿瘤发起和进展机制主要通过体外癌细胞系和动物模型进行研究。然而，传统细胞培养方法常常导致基因组变异的强烈选择，这些变异不再反映原始肿瘤在转移行为或治疗反应方面的真实情况。因此，本研究旨在探索和评估类器官技术在胃肠道癌症研究中的应用，尤其是在建模肿瘤的发起、转移进展及治疗反应等方面的价值。

2. 主要方法和发现 ​

研究综述了目前关于胃肠道癌症（包括结直肠癌、胃癌、食管癌、肝癌和胰腺癌）类器官模型的文献，强调了类器官技术在保留肿瘤及相应正常组织的遗传、表型和行为特征方面的优势。类器官培养能够更好地预测个体患者的治疗结果，这为个性化医疗提供了有力支持。尽管类器官技术展现出诸多优势，但当前模型仍存在一定的局限性。

3. 核心结论 ​

类器官技术作为一种新的肿瘤模型，能够更准确地反映胃肠道癌症的生物学特性及其对治疗的反应。相较于传统方法，类器官模型在预测治疗效果及研究肿瘤进展中显示出更高的潜力。然而，现有的类器官模型仍需进一步优化，以解决其在实验条件、培养环境以及与微环境相互作用等方面的不足。

4. 研究意义和影响 ​

本研究的意义在于强调了类器官技术在基础研究和转化研究中的重要性，尤其是在新药开发和个性化医学领域。通过改进类器官模型，研究人员可以更深入地理解胃肠道癌症的复杂性，从而推动个体化治疗的进展。这不仅有助于提高患者的治疗效果，还有望降低胃肠道癌症的相关死亡率，为公共健康提供新的解决方案。

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  1. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. - Jesus M Banales;Jose J G Marin;Angela Lamarca;Pedro M Rodrigues;Shahid A Khan;Lewis R Roberts;Vincenzo Cardinale;Guido Carpino;Jesper B Andersen;Chiara Braconi;Diego F Calvisi;Maria J Perugorria;Luca Fabris;Luke Boulter;Rocio I R Macias;Eugenio Gaudio;Domenico Alvaro;Sergio A Gradilone;Mario Strazzabosco;Marco Marzioni;Cédric Coulouarn;Laura Fouassier;Chiara Raggi;Pietro Invernizzi;Joachim C Mertens;Anja Moncsek;Sumera I. Ilyas;Julie Heimbach;Bas Groot Koerkamp;Jordi Bruix;Alejandro Forner;John Bridgewater;Juan W Valle;Gregory J Gores - Nature reviews. Gastroenterology & hepatology (2020)
  2. Three-Dimensional Culture Systems in Gastric Cancer Research. - George Alzeeb;Jean-Philippe Metges;Laurent Corcos;Catherine Le Jossic-Corcos - Cancers (2020)
  3. Beyond just a tight fortress: contribution of stroma to epithelial-mesenchymal transition in pancreatic cancer. - Ashenafi Bulle;Kian-Huat Lim - Signal transduction and targeted therapy (2020)
  4. Human Intestinal Tissue Explant Exposure to Silver Nanoparticles Reveals Sex Dependent Alterations in Inflammatory Responses and Epithelial Cell Permeability. - Kuppan Gokulan;Katherine Williams;Sarah Orr;Sangeeta Khare - International journal of molecular sciences (2020)
  5. Gut microbiota: impacts on gastrointestinal cancer immunotherapy. - Harry Cheuk Hay Lau;Joseph Jao-Yiu Sung;Jun Yu - Gut microbes (2021)
  6. miR-335-5p suppresses gastric cancer progression by targeting MAPK10. - Yi Gao;Yanfeng Wang;Xiaofei Wang;Changan Zhao;Fenghui Wang;Juan Du;Huahua Zhang;Haiyan Shi;Yun Feng;Dan Li;Jing Yan;Yan Yao;Weihong Hu;Ruxin Ding;Mengjie Zhang;Lumin Wang;Chen Huang;Jing Zhang - Cancer cell international (2021)
  7. Challenges and Opportunities in NUT Carcinoma Research. - Maxwell C Hakun;Bin Gu - Genes (2021)
  8. Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research. - Fahriye Duzagac;Gloria Saorin;Lorenzo Memeo;Vincenzo Canzonieri;Flavio Rizzolio - Cancers (2021)
  9. Organoids Are Limited in Modeling the Colon Adenoma-Carcinoma Sequence. - Yoshihisa Tokumaru;Masanori Oshi;Ankit Patel;Wanqing Tian;Li Yan;Nobuhisa Matsuhashi;Manabu Futamura;Kazuhiro Yoshida;Kazuaki Takabe - Cells (2021)
  10. Wogonoside promotes apoptosis and ER stress in human gastric cancer cells by regulating the IRE1α pathway. - Qian Gu;Canhong Zhu;Xi Wu;Lianghuan Peng;Genya Huang;Rong Hu - Experimental and therapeutic medicine (2021)

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