Responsible for nearly all deaths from solid tumors, the capacity to accurately model metastasis in vivo is essential to improving cancer survival. Our group (RW) has developed a transparent adult zebrafish, casper, that offers very high sensitivity for imaging each of the steps of metastasis [ 53]. Combining the optical superiority of this model with all of the other PFT�� cell line key technologies (transgenesis, transplantation, chemical screens, CRISPr’s), and with the pool of available mutants generated from the Zebrafish Mutation

Project [ 54], the zebrafish offers a completely unique model in which to deeply probe the biology of metastasis. A click here few studies (e.g. the discovery of SETDB1 in melanoma [28••] as mentioned above) have just begun to explore how the zebrafish can be used to understand epigenetic contributions to cancer. This clearly emerging field will greatly benefit from the genetic and chemical screening tools available in the

fish. Improvements in performing core biochemical techniques (i.e. ChIP-seq, methyl-seq, RNA-seq) along with zebrafish cell lines and antibodies will potentially allow for probing of how epigenetic changes contribute to cancer phenotypes. Rapid and large-scale transgenesis, particularly with inducible systems, will be a key method to determine the temporal dynamics of such changes, which will differ from purely Interleukin-2 receptor genetic changes seen in many tumor types. As we enter the post-genomics era, the stage is set for zebrafish researchers to capitalize on the strengths of this model system and make significant contributions to cancer research. Already, zebrafish have shown great potential through proof-of-principle experiments involving high-throughput screening [18••, 23•, 28•• and 30••] and detailed live imaging [17, 31, 33 and 34]

of embryonic and adult phenotypes. New genomic technologies have provided greater resolution for performing analyses of zebrafish cancer but require careful application and interpretation. In order to fully maximize the potential of zebrafish in cancer research, strategic areas, such as systematic and scalable methods of functional gene interrogation, using the multitude of existing models, should become a priority. Such focused efforts will inevitably lead zebrafish toward an impact on cancer research that is far more vital and productive. Papers of particular interest, published within the period of review, have been highlighted as: • of special interest We would like to thank Chris Dooley for critically reading the manuscript; Niccolò Bolli for useful discussions and Felix Krüger for providing the chemical structures in Figure 1. JY and DLS are supported by the Wellcome Trust.