Journal
DISEASE MODELS & MECHANISMS
Volume 7, Issue 7, Pages 745-754Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dmm.015784
Keywords
Cancer; Drug screening; Microenvironment; Xenotransplantation; Zebrafish
Categories
Funding
- Collaborative Health Research Project from the Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council [CPG-12-10-29/CHRP-41-38-59]
- C17 Canadian Pediatric Hematology/Oncology Network/Ewing's Cancer Foundation of Canada Grant
- Cancer Care Nova Scotia Peggy Davison Clinician Scientist Award
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The current preclinical pipeline for drug discovery can be cumbersome and costly, which limits the number of compounds that can effectively be transitioned to use as therapies. Chemical screens in zebrafish have uncovered new uses for existing drugs and identified promising new compounds from large libraries. Xenotransplantation of human cancer cells into zebrafish embryos builds on this work and enables direct evaluation of patient-derived tumor specimens in vivo in a rapid and cost-effective manner. The short time frame needed for xenotransplantation studies means that the zebrafish can serve as an early preclinical drug screening tool and can also help personalize cancer therapy by providing real-time data on the response of the human cells to treatment. In this Review, we summarize the use of zebrafish embryos in drug screening and highlight the potential for xenotransplantation approaches to be adopted as a preclinical tool to identify and prioritize therapies for further clinical evaluation. We also discuss some of the limitations of using zebrafish xenografts and the benefits of using them in concert with murine xenografts in drug optimization.
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