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A human vascularized microtumor model of patient-derived colorectal cancer recapitulates clinical disease.


ABSTRACT: Accurately 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.

SUBMITTER: Hachey SJ 

PROVIDER: S-EPMC10593408 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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A human vascularized microtumor model of patient-derived colorectal cancer recapitulates clinical disease.

Hachey Stephanie J SJ   Sobrino Agua A   Lee John G JG   Jafari Mehraneh D MD   Klempner Samuel J SJ   Puttock Eric J EJ   Edwards Robert A RA   Lowengrub John S JS   Waterman Marian L ML   Zell Jason A JA   Hughes Christopher C W CCW  

Translational research : the journal of laboratory and clinical medicine 20221205


Accurately 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-d  ...[more]

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