Study of the effect of antitumor drugs in a zebrafish xenotransplantation model

Introduction

Zebrafish is thoroughly used in Academia for investigating multiple therapeutic areas and its use is extending in industry, during the preclinical phase of drug discovery, as a quick and cost-effective research tool. Regarding oncology, it has been observed that multiple signaling pathways involved in developmental processes are coopted during carcinogenesis. It has also been shown that zebrafish can develop tumors as a result of the exposure to carcinogenic substances and of genetic mutations.

Materials and methods

Our ZeOncoTest proposes the use of zebrafish larvae as hosts for human tumor cells – xenotransplantation – for testing new drugs. Tumor cells are fluorescently labeled and injected in two days post fertilization embryos. Imaging is performed, thanks to the transparency of the larvae, at two time points (tp1 and tp2). Between tp1 and tp2, injected embryos are incubated with candidate drugs to study different possible cytotoxic and anti-metastatic effects.

Results and discussion

We have developed an automated method for imaging and analysis that allows a middle-throughput assay, approximately 10 drugs tested per month. We are currently improving the throughput. Finally, we are extending the experimental and technological development of the ZeOncoTest to the study of the cancer stem cells (CSCs) population.

Conclusion

The ZeOncoTest will be offered to the biomedical community and pharmaceutical companies to perform efficacy trials of new anticancer molecules. Moreover, it could also be adapted to inject patients’ biopsies in order to achieve a precise diagnostic tool to help the oncology team in choosing the best personalized treatment.