Anin vitrovascularized micro-tumor model of human colorectal cancer recapitulatesin vivoresponses to standard-of-care therapy
Open Access
- 19 February 2021
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Lab on a Chip
- Vol. 21 (7), 1333-1351
- https://doi.org/10.1039/d0lc01216e
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.Funding Information
- Edwards Lifesciences
- Chao Family Comprehensive Cancer Center (P30A062203)
- National Institutes of Health (CA217378, CA180122, TR-000481)
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