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.
Highlights
In the last four decades, a significant amount of time and money have been invested into the investigation of cancer
Many of the hurdles posed by unknown tumor driver mutations or treatment resistance could be partially overcome by patient-derived cancer cell xenotransplantation (PDX) followed by whole-animal high-throughput small molecule screening
In this review we will provide an insight into zebrafish models of cancer, focusing on genetic modeling of cancer in zebrafish, on recent research progress in transplantation studies, and small molecule drug screening models; and on novel approaches in modeling tumor growth in zebrafish, for example by using transgene electroporation in adult zebrafish (TEAZ) [32]
Summary
In the last four decades, a significant amount of time and money have been invested into the investigation of cancer. Many of the hurdles posed by unknown tumor driver mutations or treatment resistance could be partially overcome by patient-derived cancer cell xenotransplantation (PDX) followed by whole-animal high-throughput small molecule screening. Another drawback of the murine model, for PDX, is the fact that the tumor graft needs to be transplanted into an immunocompromised adult recipient [5,6,7]. In this review we will provide an insight into zebrafish models of cancer, focusing on genetic modeling of cancer in zebrafish, on recent research progress in transplantation studies, and small molecule drug screening models; and on novel approaches in modeling tumor growth in zebrafish, for example by using transgene electroporation in adult zebrafish (TEAZ) [32]. Human whole-genome sequencing has revealed recurrent somatic mutations in many genes encoding epigenetic regulators, several of them were found to be associated with specific cancer types [34,35,36]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have