Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening
Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening
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DOI：
10.1038/s41467-019-11867-6
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发表时间：
2019-09-05
影响因子：
16.6
通讯作者：
Jang, Se Jin
中科院分区：
文献类型：
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作者：
Kim, Minsuh;Mun, Hyemin;Jang, Se Jin
肺癌在个体之间显示出巨大的遗传和表型异质性，这推动了对个性化药物的需求。在这里，我们报告了从患者组织建立的肺癌类器官和正常支气管类器官，包括肺癌的五种组织学亚型和非肿瘤性支气管粘膜作为代表个体患者的体外模型。肺癌类器官概括了原发性肺肿瘤的组织结构，并在体外长期扩增期间保持原始肿瘤的基因组改变。正常支气管类器官维持正常支气管粘膜的细胞成分。肺癌类器官对药物的反应基于其基因组改变：BRCA 2突变型类器官对奥拉帕尼，EGFR突变型类器官对厄洛替尼，EGFR突变型/MET扩增型类器官对克唑替尼。考虑到从类器官建立到药物测试的时间较短，我们新开发的模型可能有助于通过体外患者特异性药物试验预测患者特异性药物反应。
Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalised medicine. Here, we report lung cancer organoids and normal bronchial organoids established from patient tissues comprising five histological subtypes of lung cancer and non-neoplastic bronchial mucosa as in vitro models representing individual patient. The lung cancer organoids recapitulate the tissue architecture of the primary lung tumours and maintain the genomic alterations of the original tumours during long-term expansion in vitro. The normal bronchial organoids maintain cellular components of normal bronchial mucosa. Lung cancer organoids respond to drugs based on their genomic alterations: a BRCA2-mutant organoid to olaparib, an EGFR-mutant organoid to erlotinib, and an EGFR-mutant/MET-amplified organoid to crizotinib. Considering the short length of time from organoid establishment to drug testing, our newly developed model may prove useful for predicting patient-specific drug responses through in vitro patient-specific drug trials.