Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong.
UMC Utrecht Cancer Center, Utrecht Platform for Organoid Technology, Utrecht University, Utrecht, Netherlands.
Nat Rev Gastroenterol Hepatol. 2020 Apr;17(4):203-222. doi: 10.1038/s41575-019-0255-2. Epub 2020 Feb 25.
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.
癌症是全球主要的公共卫生问题之一。胃肠道癌约占全球癌症总发病率和死亡率的三分之一。从历史上看，胃肠道肿瘤发生和发展的机制是通过体外癌细胞系和动物模型进行研究的。传统的细胞培养方法与异常基因组变异的强烈选择有关，这些变异在转移行为或对治疗的反应方面不再反映原始肿瘤。类器官技术的出现为培养胃肠道肿瘤及其相应的正常组织提供了一种强大的替代方法，保留了它们的遗传、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治疗结果方面具有重要价值。本文综述了目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）的类器官模型的文献，并讨论了它们在模拟肿瘤发生、转移进展和治疗反应方面的价值。我们还探讨了当前类器官模型的局限性，并讨论了如何改进它们，以最大限度地为未来的基础和转化研究，特别是药物发现和个性化医学领域提供帮助。
