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

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 and Se Jin Jang ()
Additional contact information
Minsuh Kim: Asan Institute for Life Sciences
Hyemin Mun: Asan Institute for Life Sciences
Chang Oak Sung: Asan Institute for Life Sciences
Eun Jeong Cho: Asan Institute for Life Sciences
Hye-Joon Jeon: Asan Institute for Life Sciences
Sung-Min Chun: Asan Institute for Life Sciences
Da Jung Jung: Asan Institute for Life Sciences
Tae Hoon Shin: Asan Institute for Life Sciences
Gi Seok Jeong: Asan Institute for Life Sciences
Dong Kwan Kim: University of Ulsan College of Medicine
Eun Kyung Choi: University of Ulsan College of Medicine
Seong-Yun Jeong: University of Ulsan College of Medicine
Alison M. Taylor: Harvard Medical School
Sejal Jain: Harvard Medical School
Matthew Meyerson: Harvard Medical School
Se Jin Jang: Asan Institute for Life Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11867-6

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