Validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response

Abstract Lung cancer rates are rising globally and non-small cell lung cancer (NSCLC) has a five year survival rate of only 24%. Unfortunately, the development of drugs to treat cancer is severely hampered by the inefficiency of translating pre-clinical studies into clinical benefit. Thus, we sought...

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Autores principales:	Devin G. Roller, Stephen A. Hoang, Kristopher D. Rawls, Katherine A. Owen, Michael B. Simmers, Robert A. Figler, Julia D. Wulfkuhle, Emanuel F. Petricoin, Brian R. Wamhoff, Daniel Gioeli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8c42edff85c244b88abc08fd238c4aa8
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spelling	oai:doaj.org-article:8c42edff85c244b88abc08fd238c4aa82021-12-02T13:34:32ZValidation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response10.1038/s41598-021-84612-z2045-2322https://doaj.org/article/8c42edff85c244b88abc08fd238c4aa82021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84612-zhttps://doaj.org/toc/2045-2322Abstract Lung cancer rates are rising globally and non-small cell lung cancer (NSCLC) has a five year survival rate of only 24%. Unfortunately, the development of drugs to treat cancer is severely hampered by the inefficiency of translating pre-clinical studies into clinical benefit. Thus, we sought to apply a tumor microenvironment system (TMES) to NSCLC. Using microvascular endothelial cells, lung cancer derived fibroblasts, and NSCLC tumor cells in the presence of in vivo tumor-derived hemodynamic flow and transport, we demonstrate that the TMES generates an in-vivo like biological state and predicts drug response to EGFR inhibitors. Transcriptomic and proteomic profiling indicate that the TMES recapitulates the in vivo and patient molecular biological state providing a mechanistic rationale for the predictive nature of the TMES. This work further validates the TMES for modeling patient tumor biology and drug response indicating utility of the TMES as a predictive tool for drug discovery and development and potential for use as a system for patient avatars.Devin G. RollerStephen A. HoangKristopher D. RawlsKatherine A. OwenMichael B. SimmersRobert A. FiglerJulia D. WulfkuhleEmanuel F. PetricoinBrian R. WamhoffDaniel GioeliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Devin G. Roller Stephen A. Hoang Kristopher D. Rawls Katherine A. Owen Michael B. Simmers Robert A. Figler Julia D. Wulfkuhle Emanuel F. Petricoin Brian R. Wamhoff Daniel Gioeli Validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response
description	Abstract Lung cancer rates are rising globally and non-small cell lung cancer (NSCLC) has a five year survival rate of only 24%. Unfortunately, the development of drugs to treat cancer is severely hampered by the inefficiency of translating pre-clinical studies into clinical benefit. Thus, we sought to apply a tumor microenvironment system (TMES) to NSCLC. Using microvascular endothelial cells, lung cancer derived fibroblasts, and NSCLC tumor cells in the presence of in vivo tumor-derived hemodynamic flow and transport, we demonstrate that the TMES generates an in-vivo like biological state and predicts drug response to EGFR inhibitors. Transcriptomic and proteomic profiling indicate that the TMES recapitulates the in vivo and patient molecular biological state providing a mechanistic rationale for the predictive nature of the TMES. This work further validates the TMES for modeling patient tumor biology and drug response indicating utility of the TMES as a predictive tool for drug discovery and development and potential for use as a system for patient avatars.
format	article
author	Devin G. Roller Stephen A. Hoang Kristopher D. Rawls Katherine A. Owen Michael B. Simmers Robert A. Figler Julia D. Wulfkuhle Emanuel F. Petricoin Brian R. Wamhoff Daniel Gioeli
author_facet	Devin G. Roller Stephen A. Hoang Kristopher D. Rawls Katherine A. Owen Michael B. Simmers Robert A. Figler Julia D. Wulfkuhle Emanuel F. Petricoin Brian R. Wamhoff Daniel Gioeli
author_sort	Devin G. Roller
title	Validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response
title_short	Validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response
title_full	Validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response
title_fullStr	Validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response
title_full_unstemmed	Validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response
title_sort	validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8c42edff85c244b88abc08fd238c4aa8
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Validation of a multicellular tumor microenvironment system for modeling patient tumor biology and drug response

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