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通过患者衍生类器官进行胆管癌疾病建模。

Cholangiocarcinoma Disease Modelling Through Patients Derived Organoids.

机构信息

Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK.

Beatson West of Scotland Cancer Centre, Glasgow G12 0YN, UK.

出版信息

Cells. 2020 Mar 30;9(4):832. doi: 10.3390/cells9040832.

Abstract

Cancer organoids are 3D phenotypic cultures that can be established from resected or biopsy tumour samples and can be grown as mini tumours in the dish. Flourishing evidence supports the feasibility of patient derived organoids (PDO) from a number of solid tumours. Evidence for cholangiocarcinoma (CCA) PDO is still sparse but growing. CCA PDO lines have been established from resected early stage disease, advanced cancers and highly chemorefractory tumours. Cancer PDO was shown to recapitulate the 3D morphology, genomic landscape and transcriptomic profile of the source counterpart. They proved to be a valued model for drug discovery and sensitivity testing, and they showed to mimic the drug response observed in vivo in the patients. However, PDO lack representation of the intratumour heterogeneity and the tumour-stroma interaction. The efficiency rate of CCA PDO within the three different subtypes, intrahepatic, perihilar and distal, is still to be explored. In this manuscript we will review evidence for CCA PDO highlighting advantages and limitations of this novel disease model.

摘要

癌症类器官是一种 3D 表型培养物,可从切除或活检的肿瘤样本中建立,并可在培养皿中长成迷你肿瘤。越来越多的证据支持从多种实体瘤中获得患者来源的类器官(PDO)。胆管癌(CCA)PDO 的证据仍然很少,但在不断增加。已经从早期疾病、晚期癌症和高度化疗耐药的肿瘤中建立了 CCA PDO 系。癌症 PDO 被证明可以重现源对应物的 3D 形态、基因组景观和转录组特征。它们被证明是药物发现和药敏测试的有价值的模型,并且它们在体内模拟了患者观察到的药物反应。然而,PDO 缺乏肿瘤内异质性和肿瘤-基质相互作用的代表性。CCA PDO 在三种不同亚型(肝内、肝门周围和远端)中的效率仍有待探索。在本文中,我们将回顾 CCA PDO 的证据,强调这种新型疾病模型的优势和局限性。

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