Advancing Pediatric Cancer Research Through Innovative Tumour Modelling

Pediatric cancer research is rapidly evolving, driven by a deep commitment to developing treatments that are not only more effective but also gentler on young patients. At the heart of this progress is the growing use of advanced tumour modelling systems – methods that replicate the complex biological conditions of childhood cancer more accurately than traditional ones.

“Tumours are not just isolated masses of mutated cells,” explains Donna Senger, Senior Investigator at Lady Davis Institute for Medical Research and Associate Professor in the Department of Oncology at McGill University. “The tumour microenvironment – the surrounding immune cells, blood vessels, and connective tissue – actively influences how cancer grows and responds to therapies.” Traditional methods, she notes, often fall short by studying cancer cells in isolation, which fail to capture these complex interactions.

To address this gap, researchers are using sophisticated mice, zebrafish, and chick embryos to implant patient tumour samples to create unique animal models of a given patient’s tumour. This allows researchers to test treatments for specific patient tumours in a setting that reflects real biological environments. For example, mice provide a living system with blood flow and normal cells, offering a more accurate picture of how tumours behave in the human body.

Nadine Azzam, Project Manager, Tumour Modelling Platform in Jason Berman’s lab at CHEO, focuses on zebrafish models, which offer unique advantages. “Because zebrafish embryos are transparent with a partially developed immune system, we can observe tumour cell growth and interactions in real-time without the need for immunosuppression,” she explains. “We also need only small amounts of tumour cells, which is crucial when biopsy material is limited.” However, she adds, “While drug delivery in zebrafish differs from humans – making it challenging to translate dosing directly – zebrafish share approximately 70% genetic similarity to humans and allow us to observe treatment responses within 7-10 days.”

Experts agree that no single animal model (model system) can capture every aspect of pediatric cancer biology. This is why integrating multiple models is a robust approach. Comparing results across these systems helps identify therapies that are more likely to be effective in each child and taking into account their unique cancer profile. Through the Pediatric Preclinical Modelling Program, ACCESS support is helping link researchers and expert capacity at sites with clinicians across the country to enable rapid, tailored testing of therapies across multiple model systems. This will allow researchers and clinicians to identify more targeted treatments that are likely to improve outcomes and reduce side effects.

This modelling approach is especially important given the rarity of many pediatric cancers. Stacey Farrand, a parent and advocate involved in the project, shares the emotional reality behind the research. “When your child is diagnosed, you feel desperate for treatments that actually work – yet many available drugs are decades old and not designed for kids,” she says. Stacey stresses that limited funding with only 4 to 7 percent of cancer research dollars directed to pediatric cases, hampers progress. “Innovative tumour models give researchers a better chance to quickly identify therapies that have the potential to directly target a specific patient’s tumor. That’s why we need to actively advocate for awareness and funding to accelerate this work.”

The choice of model depends heavily on the urgency of the clinical situation and the amount of tumour material available. “For instance, mouse models provide valuable tumour expansion, but the process can take months, which might be too slow for patients in urgent need of treatment decisions,” says James Lim, Associate Professor at the University of British Columbia. “On the other hand, chicken egg xenograft models offer rapid testing in just one to two weeks, though they require more initial tumour cells. Zebrafish models occupy a middle ground in terms of speed, material requirements, and are particularly useful for testing drug effects.”

James shared examples where their coordinated approach has directly influenced patient care. “In one rare tumour case, proteomic analysis and tumour modelling identified a metabolic pathway targetable by an already approved antidepressant, leading to a treatment option for a patient with otherwise no alternatives,” he noted. Although such successes are still emerging, they demonstrate the tangible clinical potential of these research efforts. Conversely, not all results lead to actionable treatments. In another instance involving leukemia with a known genetic mutation suggesting sensitivity to a particular drug, testing revealed no actual response in the patient-derived tumour, helping clinicians avoid ineffective therapies and save valuable time – no evidence is still evidence in the science world.

For this reason, tumour modelling isn’t just a research tool, it’s the bridge between the lab and real-world treatments. By improving how tumours are studied, these models ensure that pediatric cancer patients don’t just receive care, they receive the right care. And with advocates like Stacey calling for increased awareness and funding, the future looks hopeful. “Every child deserves a treatment plan built around their unique cancer biology and their life,” says Jason Berman, CEO and Scientific Director of the CHEO Research Institute and Vice-President of Research at CHEO. “But this kind of precision depends on having reliable, biologically accurate models.”

Future directions for this program include expanding beyond animal models into organoid cultures; three-dimensional cell systems that more closely mimic tumour behaviour in the body. Though current organoid protocols are primarily based on adult epithelial tumours, adapting these for pediatric cancers could accelerate drug testing and reduce reliance on animal models. There are still many hurdles to overcome, including limited tumour material, diverse cancer types, and logistics, yet the commitment to improving outcomes for children with cancer drives the ongoing effort.

With the support of a pan-Canadian team of experts, ACCESS is working to drive towards a world where every pediatric cancer case can be rapidly modelled and tested for optimal therapies and integrating preclinical research seamlessly into clinical decision-making. Researchers are optimistic that this future is within reach, marking a hopeful path towards more personalized, effective cancer care for all children in Canada.