title: Hooking the big one: the potential of zebrafish xenotransplantation to reform cancer drug screening in the genomic era.
abstract: 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.
authors: Department of Pediatrics, IWK Health Centre, PO Box 9700, 5850/5980 University Avenue, Halifax, NS, B3K 6R8, Canada. Life Sciences Research Institute, Faculty of Medicine, Dalhousie University, 1348 Summer Street, Halifax, NS, B3H 4R2, Canada.
authors: Chansey J
authors: CJ
authors: Veinotte
authors: Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS, B3H 4R2.
authors: Graham
authors: G
authors: Dellaire
authors: Department of Pediatrics, IWK Health Centre, PO Box 9700, 5850/5980 University Avenue, Halifax, NS, B3K 6R8, Canada. Life Sciences Research Institute, Faculty of Medicine, Dalhousie University, 1348 Summer Street, Halifax, NS, B3H 4R2, Canada. Department of Pathology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS, B3H 4R2. Department of Microbiology and Immunology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, Halifax, NS, B3H 4R2, Canada. jason.berman@iwk.nshealth.ca.
authors: Jason N
authors: JN
authors: Berman
mesh_terms: D000818:Animals; D004354:Drug Screening Assays, Antitumor; D023281:Genomics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment; D015027:Zebrafish / Q000235:genetics*
keywords: Cancer; Drug screening; Microenvironment; Xenotransplantation; Zebrafish