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

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

doi:10.1038/s41467-019-11867-6

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.

Highlights

Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalised medicine
To establish lung cancer organoids (LCOs) from LC tissues, we developed a 3D culture protocol in Matrigel (Corning, NY, USA) using minimum basal medium (MBM), which is a suboptimal media inhibiting growth of normal cell due to depletion of Wnt3a and Noggin
MBM was modified from the media for lung tumour initiating cells containing epidermal growth factor (EGF), basic fibroblast growth factor and N2 supplement for insulin and transferrin[32,33]

Summary

Introduction

Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalised medicine. Tissue-specific stem cells derived from several adult human organs, such as colon[11], stomach[12], liver[13], pancreas[13], and lung[14], have been cultured in 3D conditions using hydrogel with collagen or other ECM components, such as Matrigel. In these conditions, cells proliferate and give rise to differentiated progeny that undergo self-organisation[15]. Cancer organoids require less time to become established than

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Conclusion