Childhood Cancer Advances: DNA Fingerprints of Treatment and Global Medicine Access

Researchers at St. Jude Children’s Research Hospital have identified how lifesaving childhood cancer treatments leave "fingerprints" on DNA that can lead to second neoplasms decades later, a discovery that may improve surveillance and early detection for survivors. The findings, published in Cancer Discovery, establish a direct molecular connection between specific pediatric cancer therapies and subsequent cancers. Meanwhile, the Global Platform for Access to Childhood Cancer Medicines, a partnership between participating countries, St. Jude and the World Health Organization, is building momentum by helping countries like Nepal and Ghana strengthen pediatric cancer care through new data infrastructure.

The St. Jude researchers analyzed genetic mutations in subsequent neoplasm tumor tissue from 160 survivors who developed breast, thyroid malignancies and meningiomas, searching for patterns tied to earlier treatments. They found that radiation and chemotherapy treatments that cure childhood cancer leave specific mutational signatures or "fingerprints" in the DNA of second neoplasms. Radiation therapy was associated with the most frequent and largest DNA alterations, as well as the highest risk of secondary thyroid cancer. Chemotherapy agents also left identifiable signatures; nitrogen mustards and platinum-containing agents caused smaller changes in DNA, but the location of these mutations differed by drug type. For example, platinum agents sometimes preferentially mutated the gene NF2, leading to a greater risk of meningioma.

The researchers said they are the first to show direct causality between childhood cancer treatments and second neoplasms, with the DNA-mutating effects of treatments imprinted into the genomes of secondary cancers that emerged 20 to 30 years later. The findings provide a framework for improving long-term outcomes, allowing researchers to modify treatments to reduce harmful mutations, develop targeted therapies that avoid high-risk pathways, and tailor surveillance strategies based on an individual’s treatment history.

In a separate effort, the Global Platform for Access to Childhood Cancer Medicines was co-designed to expand access to quality-assured cancer medicines for children worldwide. Nepal, in the first wave of participating countries, and Ghana, in the second, developed new infrastructure to collect and manage national data on childhood cancer. Both countries have now built national cancer registries, enabling more consistent reporting and clearer insight into the distribution and burden of pediatric cancers. Although the Global Platform was launched about a year ago, making it too soon to measure long-term survival outcomes, the new data infrastructure is already influencing national planning.

In Ghana, registry data helped convey the scale of childhood cancer to policymakers and spurred the Ministry of Health to start implementing a national strategy for pediatric cancer. In Nepal, the data confirmed that geography remains an important barrier, as many children cannot travel long distances to reach a care center. Nepal intends to build at least eight additional cancer care centers and introduce The Shared Care Network Model to further decentralize cancer therapy. Hospitals will systematically collect and upload data on diagnosis, therapy, cures and treatment abandonment to the SJCARES system, a suite of tools that supports evidence-based decision-making on pediatric cancer care in resource-limited countries. Before participating in the Global Platform, both countries faced high rates of treatment abandonment and delayed diagnosis, partly due to limited availability of cancer medicines. The systems created for the program also represent an opportunity to strengthen care for many other pediatric diseases.