Cellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy

Abstract Targeting the epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) is one of the major precision medicine treatment options for lung adenocarcinoma. Due to common development of drug resistance to first‐ and second‐generation TKIs, third‐generation inhibitors, incl...

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Autores principales:	Fan Chen, Jinpeng Liu, Robert M. Flight, Kassandra J. Naughton, Alexsandr Lukyanchuk, Abigail R. Edgin, Xiulong Song, Haikuo Zhang, Kwok‐Kin Wong, Hunter N. B. Moseley, Chi Wang, Christine F. Brainson
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	alveolar bronchiolar EGFR lung cancer organoids Science Q
Acceso en línea:	https://doaj.org/article/1d70799b294842b6a8cf3f7bd6a3471b
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spelling	oai:doaj.org-article:1d70799b294842b6a8cf3f7bd6a3471b2021-11-17T08:40:31ZCellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy2198-384410.1002/advs.202101999https://doaj.org/article/1d70799b294842b6a8cf3f7bd6a3471b2021-11-01T00:00:00Zhttps://doi.org/10.1002/advs.202101999https://doaj.org/toc/2198-3844Abstract Targeting the epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) is one of the major precision medicine treatment options for lung adenocarcinoma. Due to common development of drug resistance to first‐ and second‐generation TKIs, third‐generation inhibitors, including osimertinib and rociletinib, have been developed. A model of EGFR‐driven lung cancer and a method to develop tumors of distinct epigenetic states through 3D organotypic cultures are described here. It is discovered that activation of the EGFR T790M/L858R mutation in lung epithelial cells can drive lung cancers with alveolar or bronchiolar features, which can originate from alveolar type 2 (AT2) cells or bronchioalveolar stem cells, but not basal cells or club cells of the trachea. It is also demonstrated that these clones are able to retain their epigenetic differences through passaging orthotopically in mice and crucially that they have distinct drug vulnerabilities. This work serves as a blueprint for exploring how epigenetics can be used to stratify patients for precision medicine decisions.Fan ChenJinpeng LiuRobert M. FlightKassandra J. NaughtonAlexsandr LukyanchukAbigail R. EdginXiulong SongHaikuo ZhangKwok‐Kin WongHunter N. B. MoseleyChi WangChristine F. BrainsonWileyarticlealveolarbronchiolarEGFRlung cancerorganoidsScienceQENAdvanced Science, Vol 8, Iss 22, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	alveolar bronchiolar EGFR lung cancer organoids Science Q
spellingShingle	alveolar bronchiolar EGFR lung cancer organoids Science Q Fan Chen Jinpeng Liu Robert M. Flight Kassandra J. Naughton Alexsandr Lukyanchuk Abigail R. Edgin Xiulong Song Haikuo Zhang Kwok‐Kin Wong Hunter N. B. Moseley Chi Wang Christine F. Brainson Cellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy
description	Abstract Targeting the epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) is one of the major precision medicine treatment options for lung adenocarcinoma. Due to common development of drug resistance to first‐ and second‐generation TKIs, third‐generation inhibitors, including osimertinib and rociletinib, have been developed. A model of EGFR‐driven lung cancer and a method to develop tumors of distinct epigenetic states through 3D organotypic cultures are described here. It is discovered that activation of the EGFR T790M/L858R mutation in lung epithelial cells can drive lung cancers with alveolar or bronchiolar features, which can originate from alveolar type 2 (AT2) cells or bronchioalveolar stem cells, but not basal cells or club cells of the trachea. It is also demonstrated that these clones are able to retain their epigenetic differences through passaging orthotopically in mice and crucially that they have distinct drug vulnerabilities. This work serves as a blueprint for exploring how epigenetics can be used to stratify patients for precision medicine decisions.
format	article
author	Fan Chen Jinpeng Liu Robert M. Flight Kassandra J. Naughton Alexsandr Lukyanchuk Abigail R. Edgin Xiulong Song Haikuo Zhang Kwok‐Kin Wong Hunter N. B. Moseley Chi Wang Christine F. Brainson
author_facet	Fan Chen Jinpeng Liu Robert M. Flight Kassandra J. Naughton Alexsandr Lukyanchuk Abigail R. Edgin Xiulong Song Haikuo Zhang Kwok‐Kin Wong Hunter N. B. Moseley Chi Wang Christine F. Brainson
author_sort	Fan Chen
title	Cellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy
title_short	Cellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy
title_full	Cellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy
title_fullStr	Cellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy
title_full_unstemmed	Cellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy
title_sort	cellular origins of egfr‐driven lung cancer cells determine sensitivity to therapy
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/1d70799b294842b6a8cf3f7bd6a3471b
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Cellular Origins of EGFR‐Driven Lung Cancer Cells Determine Sensitivity to Therapy

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