Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening

患者来源的肺癌类器官作为体外癌症模型用于治疗筛选

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作者:Minsuh Kim ,Hyemin Mun ,Chang Oak Sung ,Eun Jeong Cho ,Hye-Joon Jeon ,Sung-Min Chun ,Da Jung Jung ,Tae Hoon Shin ,Gi Seok Jeong ,Dong Kwan Kim ,Eun Kyung Choi ,Seong-Yun Jeong ,Alison M Taylor ,Sejal Jain ,Matthew Meyerson ,Se Jin Jang

Abstract

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.

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