A study led by The Hospital for Sick Children (SickKids), published in Nature, found that nearly half of childhood tumors treated with common chemotherapies carried detectable DNA changes linked to treatment within 18 months. Researchers say these changes could help clinicians spot treatment resistance earlier, allowing more precise use of chemotherapy.
Researchers examined more than 600 tumors from 544 patients across Canada, Australia and the United States, combining whole genome sequencing with medical records and computational methods developed at SickKids. The team identified distinct genomic signatures left by different chemotherapies, some visible as early as 91 days after treatment began.
“There’s a long-standing belief that pediatric cancers are genetically quiet because they haven’t had much time to mutate,” said lead author Adam Shlien. “Instead, it was mind-blowing to see how many mutations found in tumors that had relapsed or spread were linked to the chemotherapy used to treat the cancer in the first place.”
Platinum-based chemotherapy, given to nearly half of all treated cancer patients, showed a notable effect: 48% of tumors carried a detectable platinum-related signature on surviving cancer cells within 18 months.
While more than 85% of young cancer patients now survive, chemotherapy’s toxic effects can cause lifelong consequences, including heart damage or a second cancer years later. “For a young patient with their whole life ahead of them, developing a secondary cancer or cardiac issue a decade later means confronting a new, life-altering crisis in their teens or twenties,” said first author Mehdi Layeghifard.
The findings align with SickKids' Precision Child Health approach, combining genomic and treatment data to track how therapy affects a tumor over time. Layeghifard said the goal is for clinicians to use these signatures to identify patients where chemotherapy could be de-escalated, intervening as early as three months if concerning signatures appear. The team validated its findings in independent datasets that included adult patients, and Shlien said the results could have clinical value for adult cancers treated with similar drugs.
Researchers examined more than 600 tumors from 544 patients across Canada, Australia and the United States, combining whole genome sequencing with medical records and computational methods developed at SickKids. The team identified distinct genomic signatures left by different chemotherapies, some visible as early as 91 days after treatment began.
“There’s a long-standing belief that pediatric cancers are genetically quiet because they haven’t had much time to mutate,” said lead author Adam Shlien. “Instead, it was mind-blowing to see how many mutations found in tumors that had relapsed or spread were linked to the chemotherapy used to treat the cancer in the first place.”
Platinum-based chemotherapy, given to nearly half of all treated cancer patients, showed a notable effect: 48% of tumors carried a detectable platinum-related signature on surviving cancer cells within 18 months.
While more than 85% of young cancer patients now survive, chemotherapy’s toxic effects can cause lifelong consequences, including heart damage or a second cancer years later. “For a young patient with their whole life ahead of them, developing a secondary cancer or cardiac issue a decade later means confronting a new, life-altering crisis in their teens or twenties,” said first author Mehdi Layeghifard.
The findings align with SickKids' Precision Child Health approach, combining genomic and treatment data to track how therapy affects a tumor over time. Layeghifard said the goal is for clinicians to use these signatures to identify patients where chemotherapy could be de-escalated, intervening as early as three months if concerning signatures appear. The team validated its findings in independent datasets that included adult patients, and Shlien said the results could have clinical value for adult cancers treated with similar drugs.