OTTAWA, Canada – [September 24, 2025] – New research reveals that a small tropical fish can help guide personalized medicine and tailored therapies for some of the most challenging, high-risk pediatric cancer cases. Molecular profiling has transformed cancer care, but 30% of high-risk pediatric cancers do not have actionable therapeutic targets, limiting personalized treatment options and negatively affecting survival outcomes.
A first-of-its-kind proof-of-principle study , led by the Berman Lab at the CHEO Research Institute/University of Ottawa and facilitated in collaboration with two national precision oncology projects, Canada's Precision Oncology For Young peopLE (PROFYLE) (ACCESS' Driver Project) and Australia's Zero Childhood Cancer (ZERO), shows that pre-clinical zebrafish models are an effective tool to help guide clinical decision-making in real time for challenging pediatric cancer cases.
"I've dedicated my entire research career to finding better, more effective treatments for kids with cancer, so when I meet with a family to share news no parent ever wants to hear, I'm able to offer some hope," said the study's senior author Dr. Jason Berman , pediatric oncologist clinician-scientist and CEO and Scientific Director, CHEO Research Institute, and Vice-President of Research, CHEO. "Our research shows that these small tropical fish provide fast, accurate information about how a child may respond to different therapies, saving time and guiding personalized treatment decisions that have a higher likelihood of working for each child."
The larval zebrafish model holds a significant promise to improve the efficiency of evaluating personalized treatment options for the greatest number of pediatric patients with cancer, providing much-needed hope and enhancing the quality of life for kids undergoing cancer treatment.
Published in Cancer Research Communications, this study is the first to directly compare drug responses in larval zebrafish patient-derived xenograft (PDX) models and mouse PDX models with actual clinical outcomes in pediatric cancer patients.
To provide personalized cancer treatments, clinicians create PDX models from a patient's own tumour sample paired with genetic information to identify molecular targets for therapy and test possible disease-altering drugs. Mouse PDX models are currently the most widely used for this purpose but can be limited in their application and effectiveness, particularly in providing real-time clinically actionable guidance for certain high-risk cancer cases.
Larval zebrafish PDX models offer several advantages that make them particularly valuable for pediatric cancer research. They can generate drug response data more quickly and cost-effectively, while requiring only a small tumour sample, compared to mouse models.
"Every child deserves a treatment plan built around their unique cancer biology and their life," said Dr. David Malkin, Co-Chair, ACCESS, Scientific Director, PROFYLE, and Senior Staff Oncologist and Co-Lead of Precision Child Health, The Hospital for Sick Children (SickKids). "Precision tumour modelling isn't just a research tool; it's the bridge between the lab and real-world treatments to ensure that pediatric cancer patients don't just receive care, they receive the right care."
The study retrospectively examined tumour samples from 10 pediatric patients with high-risk cancers who had been enrolled on Australia's Zero Childhood Cancer program. For each of these patients, their clinical response data to individual drug or drug combinations was available, as well as in most cases, drug response data from the mouse PDX established from their tumours.
Larval zebrafish PDXs were successfully established for all patients and accurately predicted responses to 11 of 12 treatment regimens. For three kids with high-risk cancer, zebrafish models were successfully established where mouse models failed, providing robust and actionable treatment response data that mirrored the actual outcome from each child's tailored therapy. More importantly, this study supports the future use of zebrafish to model the drug responses of pediatric patients with high-risk cancers prospectively and to guide treatment decisions in real-time.
"This research demonstrates for the first time that the drug responses observed in zebrafish models closely match actual clinical outcomes and do so more rapidly and effectively than mouse modelling. The study supports the use of zebrafish models in precision medicine programs, particularly for those children for whom molecular profiling does not identify an actionable molecular target", added Dr. Michelle Haber AM, Executive Director, Children's Cancer Institute, Sydney, Australia, and co-senior author of the study. "It's a promising technique to help clinicians tailor therapies for each child's unique diagnosis."
Reference: Azzam, N., Fletcher, J. I., Melong, N., Lau, L. M. S., Dolman, E. M., Mao, J., Tax, G., Cadiz, R., Tuzi, L., Kamili, A., Dumevska, B., Xie, J., Chan, J. A., Senger, D. L., Grover, S. A., Malkin, D., Haber, M., & Berman, J. N. (2025). Modeling High-Risk Pediatric Cancers in Zebrafish to Inform Precision Therapy. Cancer research communications, 5(7), 1215–1227. https://doi.org/10.1158/2767-9764
