Clinical application of a lung cancer organoid (tumoroid) culture system

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 cultur...

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Autores principales:	Etsuko Yokota, Miki Iwai, Takuro Yukawa, Masakazu Yoshida, Yoshio Naomoto, Minoru Haisa, Yasumasa Monobe, Nagio Takigawa, Minzhe Guo, Yutaka Maeda, Takuya Fukazawa, Tomoki Yamatsuji
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9cdaa30aa00f44b393b2013acc015cd1
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spelling	oai:doaj.org-article:9cdaa30aa00f44b393b2013acc015cd12021-12-02T18:03:30ZClinical application of a lung cancer organoid (tumoroid) culture system10.1038/s41698-021-00166-32397-768Xhttps://doaj.org/article/9cdaa30aa00f44b393b2013acc015cd12021-04-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00166-3https://doaj.org/toc/2397-768XAbstract 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 BRAF G469A , TPM3-ROS1 or EGFR L858R /RB1 E737* , respectively. Targeted therapies using small molecule drugs (trametinib/erlotinib for BRAF G469A , crizotinib/entrectinib for TPM3-ROS1 and ABT-263/YM-155 for EGFR L858R /RB1 E737* ) 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.Etsuko YokotaMiki IwaiTakuro YukawaMasakazu YoshidaYoshio NaomotoMinoru HaisaYasumasa MonobeNagio TakigawaMinzhe GuoYutaka MaedaTakuya FukazawaTomoki YamatsujiNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Etsuko Yokota Miki Iwai Takuro Yukawa Masakazu Yoshida Yoshio Naomoto Minoru Haisa Yasumasa Monobe Nagio Takigawa Minzhe Guo Yutaka Maeda Takuya Fukazawa Tomoki Yamatsuji Clinical application of a lung cancer organoid (tumoroid) culture system
description	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 BRAF G469A , TPM3-ROS1 or EGFR L858R /RB1 E737* , respectively. Targeted therapies using small molecule drugs (trametinib/erlotinib for BRAF G469A , crizotinib/entrectinib for TPM3-ROS1 and ABT-263/YM-155 for EGFR L858R /RB1 E737* ) 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.
format	article
author	Etsuko Yokota Miki Iwai Takuro Yukawa Masakazu Yoshida Yoshio Naomoto Minoru Haisa Yasumasa Monobe Nagio Takigawa Minzhe Guo Yutaka Maeda Takuya Fukazawa Tomoki Yamatsuji
author_facet	Etsuko Yokota Miki Iwai Takuro Yukawa Masakazu Yoshida Yoshio Naomoto Minoru Haisa Yasumasa Monobe Nagio Takigawa Minzhe Guo Yutaka Maeda Takuya Fukazawa Tomoki Yamatsuji
author_sort	Etsuko Yokota
title	Clinical application of a lung cancer organoid (tumoroid) culture system
title_short	Clinical application of a lung cancer organoid (tumoroid) culture system
title_full	Clinical application of a lung cancer organoid (tumoroid) culture system
title_fullStr	Clinical application of a lung cancer organoid (tumoroid) culture system
title_full_unstemmed	Clinical application of a lung cancer organoid (tumoroid) culture system
title_sort	clinical application of a lung cancer organoid (tumoroid) culture system
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9cdaa30aa00f44b393b2013acc015cd1
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Clinical application of a lung cancer organoid (tumoroid) culture system

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