The zebrafish: a versatile model for both precision medicine and cancer prevention
- Jason Berman, CEO and Scientific Director Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, Ontario, Canada
There has been dramatic improvement in treatment outcomes for many pediatric cancers over the last three decades. However, for the population of young people with relapsed or refractory cancer, the prognosis remains grim. When no clear treatment options are available, a rapid in vivo preclinical platform is needed to prioritize potential therapeutic candidates. Our lab has generated a larval zebrafish xenograft platform, which can be utilized to provide personalized rapid drug response data in a clinically actionable timeframe.
This scalable platform has been employed for a variety of applications, including single and combination drug studies, novel radiotherapy trials, and chemotherapeutic-induced toxicity evaluation. Currently, this platform is being leveraged both nationally within Canada’s PRecision Oncology For Young peopLE (PROFYLE) program and internationally with a comparable Australian program known as Zero Childhood Cancer (ZCC). While targeted molecular therapies offer the potential of improved survival for hard-to-treat cancers, disease prevention is an even more desirable outcome.
Many childhood cancers arise in the context of a cancer predisposition syndrome where susceptible oncogenic mutations are harbored in the germline. Exploiting the conserved genetics and ease of genomic manipulation inherent in the zebrafish, we have applied transgenic and CRISPR-based techniques to model Li Fraumeni syndrome and a number of inherited bone marrow failure syndromes. These zebrafish models recapitulate key clinical features of the human disease, have revealed new insights into the underlying biology of cancer progression, and provided a unique in vivo platform for evaluating cancer prevention agents.