ZF-CANCER · Developing high-thoughput bioassays for human cancers in zebrafish

Recently the zebrafish has emerged as a new important system for cancer research because the zebrafish genome contains all orthologs of human oncogenes and forms tumors with similar histopathological and gene profiling features as human tumors. The zebrafish provides an in vivo vertebrate model for identifying novel mechanisms of cancer progression and for development of new anticancer compounds in a time- and cost-effective manner. The ZF-CANCER project aims to develop high-throughput bioassays for target discovery and rapid drug screenings applicable in preclinical validation pipelines. Fluorescently labelled human and zebrafish cancer cells will be implanted (xenogenic and allogenic transplantation) into zebrafish embryos transgenic for a GFP-vascular marker and quantitative, multi-colour fluorescent intravital bio-imaging of tumour progression will be set up as the readout. Because of its amenability to genetic manipulation and optical transparency, the zebrafish is currently the only vertebrate model that allows the simultaneous in vivo imaging of all hallmarks of cancer progression including cell survival, proliferation, migration and induction of angiogenesis. The combination of visual, non- invasive monitoring in translucent host embryos with powerful RNA interference technology, successfully developed for human cancer cells will enable identification of novel targets in a wide variety of human cancers. Automation of these fluorescent readouts will accelerate the screening process with chemical libraries to discover new compounds involved in different aspects of cancer progression and inhibition. In the case study, a selected panel of genes and lead compounds will be screened on a high-throughput platform, possibly resulting in the identification of important anti-tumour drugs relevant for human cancer therapy. Fundamental knowledge, tools and technical expertise gained from ZF-CANCER will be commercially exploited by one company and two high-tech SMEs.