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Issue 7, 2019
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Development of a multicellular pancreatic tumor microenvironment system using patient-derived tumor cells

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Abstract

The development of drugs to treat cancer is hampered by the inefficiency of translating pre-clinical in vitro monoculture and mouse studies into clinical benefit. There is a critical need to improve the accuracy of evaluating pre-clinical drug efficacy through the development of more physiologically relevant models. In this study, a human triculture 3D in vitro tumor microenvironment system (TMES) was engineered to accurately mimic the tumor microenvironment. The TMES recapitulates tumor hemodynamics and biological transport with co-cultured human microvascular endothelial cells, pancreatic ductal adenocarcinoma, and pancreatic stellate cells. We demonstrate that significant tumor cell transcriptomic changes occur in the TMES that correlate with the in vivo xenograft and patient transcriptome. Treatment with therapeutically relevant doses of chemotherapeutics yields responses paralleling the patients' clinical responses. Thus, this model provides a unique platform to rigorously evaluate novel therapies and is amenable to using patient tumor material directly, with applicability for patient avatars.

Graphical abstract: Development of a multicellular pancreatic tumor microenvironment system using patient-derived tumor cells

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Publication details

The article was received on 21 Jul 2018, accepted on 24 Dec 2018 and first published on 06 Mar 2019


Article type: Paper
DOI: 10.1039/C8LC00755A
Lab Chip, 2019,19, 1193-1204
  • Open access: Creative Commons BY-NC license
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    Development of a multicellular pancreatic tumor microenvironment system using patient-derived tumor cells

    D. Gioeli, C. J. Snow, M. B. Simmers, S. A. Hoang, R. A. Figler, J. A. Allende, D. G. Roller, J. T. Parsons, J. D. Wulfkuhle, E. F. Petricoin, T. W. Bauer and B. R. Wamhoff, Lab Chip, 2019, 19, 1193
    DOI: 10.1039/C8LC00755A

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