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

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...

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Veröffentlicht in:Scientific reports Jg. 11; H. 1; S. 5535 - 15
Hauptverfasser: Roller, Devin G., Hoang, Stephen A., Rawls, Kristopher D., Owen, Katherine A., Simmers, Michael B., Figler, Robert A., Wulfkuhle, Julia D., Petricoin, Emanuel F., Wamhoff, Brian R., Gioeli, Daniel
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 10.03.2021
Nature Publishing Group
Nature Portfolio
Schlagworte:
631/67
631/67/1612
631/67/327
631/67/70
Drug development
Endothelial cells
Epidermal growth factor receptors
Fibroblasts
Humanities and Social Sciences
Lung cancer
Microvasculature
multidisciplinary
Non-small cell lung carcinoma
Proteomics
Science
Science (multidisciplinary)
Small cell lung carcinoma
Survival
Tumor cells
Tumor microenvironment
Tumors
ISSN:2045-2322, 2045-2322
Online-Zugang:Volltext
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Zusammenfassung: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.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-84612-z