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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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Title: An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy.
Authors: Hachey SJ; Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA. cchughes@uci.edu., Movsesyan S, Nguyen QH, Burton-Sojo G, Tankazyan A, Wu J, Hoang T, Zhao D, Wang S, Hatch MM, Celaya E, Gomez S, Chen GT, Davis RT, Nee K, Pervolarakis N, Lawson DA, Kessenbrock K, Lee AP, Lowengrub J, Waterman ML, Hughes CCW
Source: Lab on a chip [Lab Chip] 2021 Apr 07; Vol. 21 (7), pp. 1333-1351. Date of Electronic Publication: 2021 Feb 19.
Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101128948 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1473-0189 (Electronic) Linking ISSN: 14730189 NLM ISO Abbreviation: Lab Chip Subsets: MEDLINE
Imprint Name(s): Original Publication: Cambridge, UK : Royal Society of Chemistry, c2001-
MeSH Terms: Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/therapeutic use , Colorectal Neoplasms*/drug therapy, Drug Evaluation, Preclinical ; Humans ; Lab-On-A-Chip Devices ; Tumor Microenvironment
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.
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Grant Information: R01 CA180122 United States CA NCI NIH HHS; U54 CA217378 United States CA NCI NIH HHS; UH2 TR000481 United States TR NCATS NIH HHS; UH3 TR000481 United States TR NCATS NIH HHS
Substance Nomenclature: 0 (Antineoplastic Agents)
Entry Date(s): Date Created: 20210219 Date Completed: 20210621 Latest Revision: 20211114
Update Code: 20221216
PubMed Central ID: PMC8525497
DOI: 10.1039/d0lc01216e
PMID: 33605955
Database: MEDLINE
Description
ISSN:1473-0189
DOI:10.1039/d0lc01216e