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Patient‐derived xenograft models of non‐small cell lung cancer for evaluating targeted drug sensitivity and resistance

Patient‐derived xenograft (PDX) models are a useful tool in cancer biology research. However, the number of lung cancer PDX is limited. In the present study, we successfully established 10 PDX, including three adenocarcinoma (AD), six squamous cell carcinoma (SQ) and one large cell carcinoma (LA), f...

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Autores principales: Kita, Kenji, Fukuda, Koji, Takahashi, Hiro, Tanimoto, Azusa, Nishiyama, Akihiro, Arai, Sachiko, Takeuchi, Shinji, Yamashita, Kaname, Ohtsubo, Koshiro, Otani, Sakiko, Yanagimura, Naohiro, Suzuki, Chiaki, Ikeda, Hiroko, Tamura, Masaya, Matsumoto, Isao, Yano, Seiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778641/
https://www.ncbi.nlm.nih.gov/pubmed/31432603
http://dx.doi.org/10.1111/cas.14171
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author Kita, Kenji
Fukuda, Koji
Takahashi, Hiro
Tanimoto, Azusa
Nishiyama, Akihiro
Arai, Sachiko
Takeuchi, Shinji
Yamashita, Kaname
Ohtsubo, Koshiro
Otani, Sakiko
Yanagimura, Naohiro
Suzuki, Chiaki
Ikeda, Hiroko
Tamura, Masaya
Matsumoto, Isao
Yano, Seiji
author_facet Kita, Kenji
Fukuda, Koji
Takahashi, Hiro
Tanimoto, Azusa
Nishiyama, Akihiro
Arai, Sachiko
Takeuchi, Shinji
Yamashita, Kaname
Ohtsubo, Koshiro
Otani, Sakiko
Yanagimura, Naohiro
Suzuki, Chiaki
Ikeda, Hiroko
Tamura, Masaya
Matsumoto, Isao
Yano, Seiji
author_sort Kita, Kenji
collection PubMed
description Patient‐derived xenograft (PDX) models are a useful tool in cancer biology research. However, the number of lung cancer PDX is limited. In the present study, we successfully established 10 PDX, including three adenocarcinoma (AD), six squamous cell carcinoma (SQ) and one large cell carcinoma (LA), from 30 patients with non‐small cell lung cancer (NSCLC) (18 AD, 10 SQ, and 2 LA), mainly in SCID hairless outbred (SHO) mice (Crlj:SHO‐Prkdc(scid)Hr(hr)). Histology of SQ, advanced clinical stage (III‐IV), status of lymph node metastasis (N2‐3), and maximum standardized uptake value ≥10 when evaluated using a delayed (18)F‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography (FDG‐PET) scan was associated with successful PDX establishment. Histological analyses showed that PDX had histology similar to that of patients’ surgically resected tumors (SRT), whereas components of the microenvironment were replaced with murine cells after several passages. Next‐generation sequencing analyses showed that after two to six passages, PDX preserved the majority of the somatic mutations and mRNA expressions of the corresponding SRT. Two out of three PDX with AD histology had epidermal growth factor receptor (EGFR) mutations (L858R or exon 19 deletion) and were sensitive to EGFR tyrosine kinase inhibitors (EGFR‐TKI), such as gefitinib and osimertinib. Furthermore, in one of the two PDX with an EGFR mutation, osimertinib resistance was induced that was associated with epithelial‐to‐mesenchymal transition. This study presented 10 serially transplantable PDX of NSCLC in SHO mice and showed the use of PDX with an EGFR mutation for analyses of EGFR‐TKI resistance.
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spelling pubmed-67786412019-10-11 Patient‐derived xenograft models of non‐small cell lung cancer for evaluating targeted drug sensitivity and resistance Kita, Kenji Fukuda, Koji Takahashi, Hiro Tanimoto, Azusa Nishiyama, Akihiro Arai, Sachiko Takeuchi, Shinji Yamashita, Kaname Ohtsubo, Koshiro Otani, Sakiko Yanagimura, Naohiro Suzuki, Chiaki Ikeda, Hiroko Tamura, Masaya Matsumoto, Isao Yano, Seiji Cancer Sci Original Articles Patient‐derived xenograft (PDX) models are a useful tool in cancer biology research. However, the number of lung cancer PDX is limited. In the present study, we successfully established 10 PDX, including three adenocarcinoma (AD), six squamous cell carcinoma (SQ) and one large cell carcinoma (LA), from 30 patients with non‐small cell lung cancer (NSCLC) (18 AD, 10 SQ, and 2 LA), mainly in SCID hairless outbred (SHO) mice (Crlj:SHO‐Prkdc(scid)Hr(hr)). Histology of SQ, advanced clinical stage (III‐IV), status of lymph node metastasis (N2‐3), and maximum standardized uptake value ≥10 when evaluated using a delayed (18)F‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography (FDG‐PET) scan was associated with successful PDX establishment. Histological analyses showed that PDX had histology similar to that of patients’ surgically resected tumors (SRT), whereas components of the microenvironment were replaced with murine cells after several passages. Next‐generation sequencing analyses showed that after two to six passages, PDX preserved the majority of the somatic mutations and mRNA expressions of the corresponding SRT. Two out of three PDX with AD histology had epidermal growth factor receptor (EGFR) mutations (L858R or exon 19 deletion) and were sensitive to EGFR tyrosine kinase inhibitors (EGFR‐TKI), such as gefitinib and osimertinib. Furthermore, in one of the two PDX with an EGFR mutation, osimertinib resistance was induced that was associated with epithelial‐to‐mesenchymal transition. This study presented 10 serially transplantable PDX of NSCLC in SHO mice and showed the use of PDX with an EGFR mutation for analyses of EGFR‐TKI resistance. John Wiley and Sons Inc. 2019-10-06 2019-10 /pmc/articles/PMC6778641/ /pubmed/31432603 http://dx.doi.org/10.1111/cas.14171 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Kita, Kenji
Fukuda, Koji
Takahashi, Hiro
Tanimoto, Azusa
Nishiyama, Akihiro
Arai, Sachiko
Takeuchi, Shinji
Yamashita, Kaname
Ohtsubo, Koshiro
Otani, Sakiko
Yanagimura, Naohiro
Suzuki, Chiaki
Ikeda, Hiroko
Tamura, Masaya
Matsumoto, Isao
Yano, Seiji
Patient‐derived xenograft models of non‐small cell lung cancer for evaluating targeted drug sensitivity and resistance
title Patient‐derived xenograft models of non‐small cell lung cancer for evaluating targeted drug sensitivity and resistance
title_full Patient‐derived xenograft models of non‐small cell lung cancer for evaluating targeted drug sensitivity and resistance
title_fullStr Patient‐derived xenograft models of non‐small cell lung cancer for evaluating targeted drug sensitivity and resistance
title_full_unstemmed Patient‐derived xenograft models of non‐small cell lung cancer for evaluating targeted drug sensitivity and resistance
title_short Patient‐derived xenograft models of non‐small cell lung cancer for evaluating targeted drug sensitivity and resistance
title_sort patient‐derived xenograft models of non‐small cell lung cancer for evaluating targeted drug sensitivity and resistance
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778641/
https://www.ncbi.nlm.nih.gov/pubmed/31432603
http://dx.doi.org/10.1111/cas.14171
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