• Stephanie J Hachey, Agua Sobrino, John G Lee, Mehraneh D Jafari, Samuel J Klempner, Eric J Puttock, Robert A Edwards, John S Lowengrub, Marian L Waterman, Jason A Zell, and HughesChristopher C WCCWIrvine Department of Molecular Biology and Biochemistry, University of California, Irvine, California; Irvine Department of Biomedical Engineering, University of California, Irvine, California. Electronic address: cchughes@uci.edu..
• Irvine Department of Molecular Biology and Biochemistry, University of California, Irvine, California.
• Transl Res. 2023 May 1; 255: 9710897-108.

AbstractAccurately modeling tumor biology and testing novel therapies on patient-derived cells is critically important to developing therapeutic regimens personalized to a patient's specific disease. The vascularized microtumor (VMT), or "tumor-on-a-chip," is a physiologic preclinical cancer model that incorporates key features of the native human tumor microenvironment within a transparent microfluidic platform, allowing rapid drug screening in vitro. Herein we optimize methods for generating patient-derived VMT (pVMT) using fresh colorectal cancer (CRC) biopsies and surgical resections to test drug sensitivities at the individual patient level. In response to standard chemotherapy and TGF-βR1 inhibition, we observe heterogeneous responses between pVMT derived from 6 patient biopsies, with the pVMT recapitulating tumor growth, histological features, metabolic heterogeneity, and drug responses of actual CRC tumors. Our results suggest that a translational infrastructure providing rapid information from patient-derived tumor cells in the pVMT, as established in this study, will support efforts to improve patient outcomes.Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

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