Zebrafish: a new companion for translational research in oncology

Abstract

In an era of high-throughput "omic" technologies, the unprecedented amount of data that can be generated presents a significant opportunity but simultaneously an even greater challenge for oncologists trying to provide personalized treatment. Classically, preclinical testing of new targets and identification of active compounds against those targets have entailed the extensive use of established human cell lines, as well as genetically modified mouse tumor models. Patient-derived xenografts in zebrafish may in the near future provide a platform for selecting an appropriate personalized therapy and together with zebrafish transgenic tumor models represent an alternative vehicle for drug development. The zebrafish is readily genetically modified. The transparency of zebrafish embryos and the recent development of pigment-deficient zebrafish afford researchers the valuable capacity to observe directly cancer formation and progression in a live vertebrate host. The zebrafish is amenable to transplantation assays that test the serial passage of fluorescently labeled tumor cells as well as their capacity to disseminate and/or metastasize. Progress achieved to date in genetic engineering and xenotransplantation will establish the zebrafish as one of the most versatile animal models for cancer research. A model organism that can be used in transgenesis, transplantation assays, single-cell functional assays, and in vivo imaging studies make zebrafish a natural companion for mice in translational oncology research.

Figure 1

Absolute number of articles for zebrafish cancer models per year of publication extracted from Pubmed database (last accessed on the 1^st November 2014; http://www.ncbi.nlm.nih.gov/pubmed/).

Figure 2

Roles of zebrafish tumor models in present and future cancer research.

Figure 3

Potential of zebrafish tumor models in co-clinical studies. Zebrafish combine the characteristics of cell lines and animal models and therefore Genetically Engineered Zebrafish Models (GEZM) and xenografts are currently used for drug screening and pre-clinical drug development. In the future, tumourgrafts inserted in zebrafish embryos and mice could be used for patient selection in clinical trials. A GEZM could be used to fill the gap whenever a mouse model does not exist GEMM: genetic engineered mouse models. PDX: patient-derived xenografts. PDXZ: patient-derived xenografts in zebrafish embryos.