An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy

Stephanie J. Hachey; Silva Movsesyan; Quy H. Nguyen; Giselle Burton-Sojo; Ani Tankazyan; Jie Wu; Tuyen Hoang; Da Zhao; Shuxiong Wang; Michaela M. Hatch; Elizabeth Celaya; Samantha Gomez; George T. Chen; Ryan T. Davis; Kevin Nee; Nicholas Pervolarakis; Devon A. Lawson; Kai Kessenbrock; Abraham P. Lee; John Lowengrub; Marian L. Waterman; Christopher C. W. Hughes

doi:10.1039/D0LC01216E

An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy†

Stephanie J. Hachey,

^a Silva Movsesyan,^a Quy H. Nguyen,^b Giselle Burton-Sojo,^a Ani Tankazyan,^a Jie Wu,^b Tuyen Hoang,^c Da Zhao,

^d Shuxiong Wang,^e Michaela M. Hatch,^a Elizabeth Celaya,^a Samantha Gomez,^a George T. Chen,

^f Ryan T. Davis,^g Kevin Nee,^b Nicholas Pervolarakis,^h Devon A. Lawson,^g Kai Kessenbrock,^b Abraham P. Lee,

^d John Lowengrub,^deh Marian L. Waterman^f and Christopher C. W. Hughes*^ad

Author affiliations

* Corresponding authors

^a Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA
E-mail: cchughes@uci.edu

^b Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA

^c Department of Biostatistics, University of California, Irvine, Irvine, CA, USA

^d Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, USA

^e Department of Mathematics, University of California, Irvine, Irvine, CA, USA

^f Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA, USA

^g Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA

^h Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, USA

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 and disease modeling tools. The vascularized micro-tumor (VMT) is a novel three-dimensional model system (tumor-on-a-chip) 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 this microphysiological system (MPS) 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 responses in the VMT more closely model CRC tumor clinicopathology than current standard drug screening modalities, including 2-dimensional monolayer culture and 3-dimensional spheroids.

This article is part of the themed collection: organ-on-a-chip systems: translating concept into practice

Lab on a Chip

An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy†

Abstract

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An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy

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