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An In Vitro Vascularized Micro-Tumor Model of Human Colorectal Cancer Recapitulates In Vivo Drug Responses

Stephanie J. Hachey, Silva Movsesyan, Quy H. Nguyen, Giselle Burton-Sojo, Ani Tankanzyan, Jie Wu, Tuyen Hoang, Michaela M. Hatch, Da Zhao, Elizabeth Celaya, Samantha Gomez, George T. Chen, Ryan T. Davis, Kevin Nee, Nicholas Pervolarakis, Devon A. Lawson, Kai Kessenbrock, Abraham P. Lee, Marian L. Waterman, Christopher C.W. Hughes
doi: https://doi.org/10.1101/2020.03.03.973891
Stephanie J. Hachey
1Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA
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Silva Movsesyan
1Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA
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Quy H. Nguyen
2Department of Biological Chemistry, University of California, Irvine, Irvine, CA, 92697, USA
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Giselle Burton-Sojo
1Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA
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Ani Tankanzyan
1Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA
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Jie Wu
2Department of Biological Chemistry, University of California, Irvine, Irvine, CA, 92697, USA
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Tuyen Hoang
3Department of Biostatistics, University of California, Irvine, Irvine, CA, 92697, USA
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Michaela M. Hatch
1Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA
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Da Zhao
4Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA
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Elizabeth Celaya
1Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA
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Samantha Gomez
1Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA
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George T. Chen
5Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA, 92697, USA
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Ryan T. Davis
6Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, 92697, USA
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Kevin Nee
2Department of Biological Chemistry, University of California, Irvine, Irvine, CA, 92697, USA
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Nicholas Pervolarakis
7Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, 92697, USA
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Devon A. Lawson
6Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, 92697, USA
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Kai Kessenbrock
2Department of Biological Chemistry, University of California, Irvine, Irvine, CA, 92697, USA
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Abraham P. Lee
4Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA
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Marian L. Waterman
5Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA, 92697, USA
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Christopher C.W. Hughes
1Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA
4Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA
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  • For correspondence: cchughes@uci.edu
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Abstract

Around 95% of anti-cancer drugs that show promise during preclinical study fail to gain FDA-approval for clinical use. This failure of the preclinical pipeline highlights the need for improved, physiologically-relevant in vitro models that can better serve as reliable drug-screening tools. The vascularized micro-tumor (VMT) is a novel three-dimensional model system that recapitulates the complex human tumor microenvironment, including perfused vasculature, within a transparent microfluidic device, allowing real-time study of drug responses and tumor-stromal interactions. Here we have validated the VMT platform for the study of colorectal cancer (CRC), the second leading cause of cancer-related deaths, by showing that gene expression, tumor heterogeneity, and treatment response in the VMT more closely model CRC tumor clinicopathology than current standard drug screening modalities, including 2-dimensional (2D) monolayer culture and 3-dimensional (3D) spheroids.

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Posted March 05, 2020.
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An In Vitro Vascularized Micro-Tumor Model of Human Colorectal Cancer Recapitulates In Vivo Drug Responses
Stephanie J. Hachey, Silva Movsesyan, Quy H. Nguyen, Giselle Burton-Sojo, Ani Tankanzyan, Jie Wu, Tuyen Hoang, Michaela M. Hatch, Da Zhao, Elizabeth Celaya, Samantha Gomez, George T. Chen, Ryan T. Davis, Kevin Nee, Nicholas Pervolarakis, Devon A. Lawson, Kai Kessenbrock, Abraham P. Lee, Marian L. Waterman, Christopher C.W. Hughes
bioRxiv 2020.03.03.973891; doi: https://doi.org/10.1101/2020.03.03.973891
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An In Vitro Vascularized Micro-Tumor Model of Human Colorectal Cancer Recapitulates In Vivo Drug Responses
Stephanie J. Hachey, Silva Movsesyan, Quy H. Nguyen, Giselle Burton-Sojo, Ani Tankanzyan, Jie Wu, Tuyen Hoang, Michaela M. Hatch, Da Zhao, Elizabeth Celaya, Samantha Gomez, George T. Chen, Ryan T. Davis, Kevin Nee, Nicholas Pervolarakis, Devon A. Lawson, Kai Kessenbrock, Abraham P. Lee, Marian L. Waterman, Christopher C.W. Hughes
bioRxiv 2020.03.03.973891; doi: https://doi.org/10.1101/2020.03.03.973891

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