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

• Published in: Lab on a chip Vol. 21; no. 7; pp. 1333 - 1351
• Main Authors: Hachey, Stephanie J, Movsesyan, Silva, Nguyen, Quy H, Burton-Sojo, Giselle, Tankazyan, Ani, Wu, Jie, Hoang, Tuyen, Zhao, Da, Wang, Shuxiong, Hatch, Michaela M, Celaya, Elizabeth, Gomez, Samantha, Chen, George T, Davis, Ryan T, Nee, Kevin, Pervolarakis, Nicholas, Lawson, Devon A, Kessenbrock, Kai, Lee, Abraham P, Lowengrub, John, Waterman, Marian L, Hughes, Christopher C. W
• Format: Journal Article
• Published: 08.04.2021
• ISSN: 1473-0197; 1473-0189
• DOI: 10.1039/d0lc01216e

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. VMTs recapitulate in vivo drug responses and also reconstitute the cellular diversity of tumors.