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.
Lab on a chip. 2020 Oct 26 [Epub ahead of print]
María Virumbrales-Muñoz, Jiong Chen, Jose Ayuso, Moonhee Lee, E Jason Abel, David J Beebe
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, USA. and University of Wisconsin Carbone Cancer Center, Wisconsin Institutes for Medical Research, 1111 Highland Ave., Madison, WI 53705, USA., Department of Biomedical Engineering, Wisconsin Institutes for Medical Research, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, USA., Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, 1111 Highland Avenue, Madison, Wisconsin 53705, USA. and University of Wisconsin Carbone Cancer Center, Wisconsin Institutes for Medical Research, 1111 Highland Ave., Madison, WI 53705, USA and Medical Engineering, Morgridge Institute for Research, 330 N Orchard street, Madison, WI 53715, USA., Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, 1111 Highland Ave., Madison, 53705 WI, USA.