Issue 23, 2020

Organotypic primary blood vessel models of clear cell renal cell carcinoma for single-patient clinical trials

Abstract

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary cancer associated with the development of abnormal tumor angiogenesis. Although multiple anti-angiogenic therapies have been developed, responses to individual treatment are highly variable between patients. Thus, the use of one-patient clinical trials has been suggested as an alternative to standard trials. We used a microfluidic device to generate organotypic primary patient-specific blood vessel models using normal (NEnC) and tumor-associated primary CD31+ selected cells (TEnC). Our model was able to recapitulate differences in angiogenic sprouting and vessel permeability that characterize normal and tumor-associated vessels. We analyzed the expression profile of vessel models to define vascular normalization in a patient-specific manner. Using this data, we identified actionable targets to normalize TEnC vessel function to a more NEnC-like phenotype. Finally, we tested two of these drugs in our patient-specific models to determine the efficiency in restoring vessel function showing the potential of the model for single-patient clinical trials.

Graphical abstract: Organotypic primary blood vessel models of clear cell renal cell carcinoma for single-patient clinical trials

Supplementary files

Article information

Article type
Paper
Submitted
12 Mar 2020
Accepted
07 Oct 2020
First published
26 Oct 2020
This article is Open Access
Creative Commons BY-NC license

Lab Chip, 2020,20, 4420-4432

Organotypic primary blood vessel models of clear cell renal cell carcinoma for single-patient clinical trials

M. Virumbrales-Muñoz, J. Chen, J. Ayuso, M. Lee, E. J. Abel and D. J. Beebe, Lab Chip, 2020, 20, 4420 DOI: 10.1039/D0LC00252F

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