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

By Minsuh Kim, Hyemin Mun, C. O. Sung, E. Cho, H. Jeon, S. Chun, D.-J. Jung, Tae Hoon Shin, G. S. Jeong, D. K. Kim and 6 more. Nature Communications, 2019

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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. The clinical efficacy of standard therapy in lung cancer is limited by high level of heterogeneity. Here, the authors report patient-derived lung cancer organoids from different histological subtypes and show them to faithfully recapitulate the histology, genomics, and drug responses of the primary lung tumours.

Subfields: Cancer Research, Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/0d2c41d581e7b3070eef701e2a6d722231bf752c