A new international study led by the Hospital for Sick Children (SickKids) found that almost half of childhood tumors treated with common types of chemotherapy showed detectable DNA changes related to treatment within 18 months. Researchers say these changes could ultimately help clinicians detect treatment resistance earlier, before cancer recurrence or metastasis, opening the door to more precise use of chemotherapy.
Published in nature, Researchers analyzed more than 600 tumors from 544 patients in Canada, Australia, and the United States. By combining whole-genome sequencing with detailed medical records and advanced computational methods developed at SickKids, the research team discovered distinct genomic signatures of DNA changes left behind by different chemotherapy treatments. Some of these patterns emerged within 91 days of treatment initiation.
There’s a long-standing idea that childhood cancers are genetically silent because they don’t have much time to mutate. Rather, it was shocking to learn that many of the mutations found in tumors that recurred or metastasized were linked to the chemotherapy used to treat the cancer in the first place. ”
Dr. Adam Schrian, first author, Genetics and Genome Biology, Senior Scientist, and Director of the Genomic Diagnostics Laboratory at SickKids
The most striking finding was the impact of platinum-based chemotherapy, which is administered to nearly half of treated cancer patients. Within 18 months of treatment, 48% of tumors had detectable platinum-related “signatures” in surviving cancer cells.
Can we reduce the risk of late effects?
Over the past 50 years, outcomes in childhood cancer have improved significantly, with more than 85 percent of young patients surviving. Still, the toxic effects of chemotherapy mean it can damage healthy cells and cause lifelong health effects, including heart damage and the risk of other cancers years later.
These “late effects” have a unique impact on children.
“For young patients who are nearing the end of their lives, developing a second cancer or heart disease in 10 years means facing a new life-altering crisis in their teens or 20s,” said lead author Mehdi Reigifard, Ph.D., a senior researcher at the Schulien Institute.
Until now, researchers do not know how much DNA damage is related to chemotherapy exposure or when and how treatment-resistant tumors develop in childhood cancers. Genomic signatures, or fingerprints, are records of how cancer cells respond to treatment, and now that researchers have recorded these unique signatures, clinicians can track them and identify cancers that are progressing in ways that make them more likely to resist treatment, metastasize, or later come back.
The research required a new level of computational analysis
In this study, the researchers performed the highly complex computational genomics required to both interpret and translate the imprint each cancer drug leaves on the genome.
“We have spent years analyzing the data and developing new computational methods to pinpoint these subtle patterns and link them to specific treatments,” said Shurian, who believes this is the world’s largest search for treatment signs in childhood cancers using whole-genome sequencing.
This study was possible because the researchers had access to detailed chemotherapy exposure information, including treatment type, dose, and timing, from a large number of families, the majority of whom were participating in the SickKids Kids Cancer Sequencing (KiCS) program.
The Gubler family in Oshawa, Ont., was one such family, shocked last spring when their son Roman was diagnosed with lymphoma after visiting Sick Kids’ emergency room with a persistent fever. He underwent successful treatment from May to September, and his lymphoma has been in remission ever since.
“When we realized what it meant to join KiCS to support the search for new treatments, we were completely on board,” says Roman’s mother, Nicole. “Despite what he had been through, Roman told me he was so proud to be able to contribute to helping other children. It would be great if my little 9-year-old son could be involved in such important research.”
Potential early warning system
The Nature study exemplifies Precision Child Health, which combines genomic information and treatment history to better understand how treatments affect a patient’s cancer over time and potentially tailor treatments to reduce toxic effects.
In fact, this finding is a rare case with multiple levels of precision.
“Every tumor is unique and driven by its own biology based on where it originates and how it evolved,” Schrian says. “When treated with chemotherapy, the interaction between the tumor and the treatment changes its composition and evolutionary pathway. Defining that interaction could allow clinicians to detect important signals of future outcome long before they become clinically visible.”
Researchers say the genomic features identified in this study could one day serve as biomarkers to create a potential early warning system for children undergoing cancer treatment.
“The ultimate goal is for clinicians to use these to identify patients who can be de-escalated from chemotherapy and intervened as early as three months if there are genomic indications,” Layeghifard says.
In the future, blood tests may be required for patients of all ages facing the need for chemotherapy. Importantly, the research team validated their findings in an independent dataset that included adult patients.
“Ultimately, we believe these findings will have tremendous clinical value for adult cancers treated with similar drugs,” says Shrian.
sauce:
hospital for sick children
Reference magazines:
Reigiffard, M. others. (2026). Previous treatment defines the mutational profile in childhood cancers at the time of recurrence. nature. DOI: 10.1038/s41586-026-10803-1. https://www.nature.com/articles/s41586-026-10803-1
