Zebrafish Models of Cancer-New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate

Abstract

Zebrafish (Danio rerio) is a valuable non-mammalian vertebrate model widely used to study development and disease, including more recently cancer. The evolutionary conservation of cancer-related programs between human and zebrafish is striking and allows extrapolation of research outcomes obtained in fish back to humans. Zebrafish has gained attention as a robust model for cancer research mainly because of its high fecundity, cost-effective maintenance, dynamic visualization of tumor growth in vivo, and the possibility of chemical screening in large numbers of animals at reasonable costs. Novel approaches in modeling tumor growth, such as using transgene electroporation in adult zebrafish, could improve our knowledge about the spatial and temporal control of cancer formation and progression in vivo. Looking at genetic as well as epigenetic alterations could be important to explain the pathogenesis of a disease as complex as cancer. In this review, we highlight classic genetic and transplantation models of cancer in zebrafish as well as provide new insights on advances in cancer modeling. Recent progress in zebrafish xenotransplantation studies and drug screening has shown that zebrafish is a reliable model to study human cancer and could be suitable for evaluating patient-derived xenograft cell invasiveness. Rapid, large-scale evaluation of in vivo drug responses and kinetics in zebrafish could undoubtedly lead to new applications in personalized medicine and combination therapy. For all of the above-mentioned reasons, zebrafish is approaching a future of being a pre-clinical cancer model, alongside the mouse. However, the mouse will continue to be valuable in the last steps of pre-clinical drug screening, mostly because of the highly conserved mammalian genome and biological processes.

Keywords: zebrafish, epigenetics, xenotransplantation, drug screen, pre-clinical cancer model.

Figure 1

Zebrafish models of cancer. Zebrafish develops cancer phenotypes similar to human cancer in different tissues and organs. All of these cancer types and their zebrafish models are discussed in Section 2. Genetic models of cancer. PNST—peripheral nerve sheath tumor; HCC—hepatocellular carcinoma; RMS—rhabdomyosarcoma; ♂—male; ♀—female.