Abstract

Despite high expectations for lung tumoroids, they have not been applied in the clinic due to the difficulty of their long-term culture. Here, however, using AO (airway organoid) media developed by the Clevers laboratory, we succeeded in generating 3 lung tumoroid lines for long-term culture (>13 months) from 41 lung cancer cases (primary or metastatic). Use of nutlin-3a was key to selecting lung tumoroids that harbor mutant p53 in order to eliminate normal lung epithelial organoids. Next-generation sequencing (NGS) analysis indicated that each lung tumoroid carried BRAFG469A, TPM3-ROS1 or EGFRL858R/RB1E737*, respectively. Targeted therapies using small molecule drugs (trametinib/erlotinib for BRAFG469A, crizotinib/entrectinib for TPM3-ROS1 and ABT-263/YM-155 for EGFRL858R/RB1E737*) significantly suppressed the growth of each lung tumoroid line. AO media was superior to 3 different media developed by other laboratories. Our experience indicates that long-term lung tumoroid culture is feasible, allowing us to identify NGS-based therapeutic targets and determine the responsiveness to corresponding small molecule drugs.

Details

Title
Clinical application of a lung cancer organoid (tumoroid) culture system
Author
Yokota Etsuko 1   VIAFID ORCID Logo  ; Iwai Miki 2 ; Yukawa Takuro 1 ; Yoshida Masakazu 3 ; Naomoto Yoshio 1 ; Haisa Minoru 4 ; Monobe Yasumasa 5 ; Takigawa Nagio 6   VIAFID ORCID Logo  ; Guo Minzhe 7 ; Maeda Yutaka 7 ; Fukazawa Takuya 1   VIAFID ORCID Logo  ; Yamatsuji Tomoki 1 

1  Kawasaki Medical School, Department of General Surgery, Okayama, Japan (GRID:grid.415086.e) (ISNI:0000 0001 1014 2000) 
2  Kawasaki Medical School, General Medical Center Research Unit, Okayama, Japan (GRID:grid.415086.e) (ISNI:0000 0001 1014 2000) 
3  Kurashiki Central Hospital, Department of Thoracic Surgery, Kurashiki, Japan (GRID:grid.415565.6) (ISNI:0000 0001 0688 6269) 
4  Kawasaki Medical School, Professor with Special Assignment, Okayama, Japan (GRID:grid.415086.e) (ISNI:0000 0001 1014 2000) 
5  Kawasaki Medical School, Department of Pathology, Okayama, Japan (GRID:grid.415086.e) (ISNI:0000 0001 1014 2000) 
6  Kawasaki Medical School, Department of General Internal Medicine 4, Okayama, Japan (GRID:grid.415086.e) (ISNI:0000 0001 1014 2000) 
7  The University of Cincinnati College of Medicine (UC-COM), Perinatal Institute, Division of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children’s Hospital Medical Center (CCHMC) and Department of Pediatrics, Cincinnati, USA (GRID:grid.24827.3b) (ISNI:0000 0001 2179 9593) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
ISSN
2397768X
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41698-021-00166-3
ProQuest document ID
2511563992
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.