Platinum-based chemotherapy drugs like cisplatin and carboplatin cause significant, hidden DNA damage in healthy tissues and can age a child’s cells by decades in a short period, according to a study published in Science by researchers at the Wellcome Sanger Institute, the University of Cambridge, the Francis Crick Institute, and King’s College London. While these treatments successfully cure childhood cancers, the genomic sequencing research provides a direct biological explanation for why childhood cancer survivors frequently face long-term health issues such as secondary cancers and liver disease later in life.
Genomic Sequencing Reveals Platinum-Based Chemotherapy DNA Damage
To investigate the under-appreciated impact of cancer treatments on the rest of the body, a research team analyzed 186 blood samples, liver tumour samples, and non-cancerous liver tissue from nine children treated with platinum-based chemotherapy, according to the study. They also examined 30 samples from two children with liver cancer who received non-platinum treatment, alongside 47 additional samples from children with other cancers or those who had not undergone treatment.
Using a cutting-edge sequencing technique called NanoSeq, scientists uncovered a much higher number of DNA changes across multiple tissues after platinum-based treatment. According to the findings, some children developed the same number of genetic changes typically seen in middle-aged adult tissues. Some of these mutations are classified as cancer drivers, which may increase the risk that surviving healthy cells will eventually develop into cancer later in life, though researchers note this complication remains very rare.
Distinctive Liver Damage and Metabolic Changes
The study uncovered a previously unseen pattern of genetic changes exclusive to liver tissues. Because this specific damage did not appear in any other tissues, researchers suggest it occurs during the breakdown of platinum-based chemotherapy drugs, a metabolic process that takes place primarily in the liver, according to study co-senior author Dr. Foad Rouhani at the Francis Crick Institute and King’s College London.
Dr. Rouhani explained that researchers found not only cancer-associated genes but also genes linked to long-term changes in liver metabolism, which may explain why childhood cancer survivors face premature aging health conditions.
Balancing Life-Saving Cancer Cures with Long-Term Survivorship
Despite the newly uncovered genetic toll, researchers emphasize that chemotherapy remains essential for curing childhood cancer and that there are currently no alternatives.
“Our study represents a milestone in revealing the DNA damage that chemotherapy causes in normal tissues,” said Dr. Anna Wenger, first author at the Wellcome Sanger Institute and the University of Gothenburg. By identifying the exact mechanisms behind this damage, scientists hope to guide future research toward developing protective treatments or next-generation chemotherapies that leave background healthy tissue largely untouched.
Establishing that normal tissue damage occurs enables healthcare providers to identify potential secondary conditions and liver pathologies much earlier in a patient’s life, according to study authors.
Frequently Asked Questions
Does this research mean children should stop receiving chemotherapy?
No. According to the study authors, chemotherapy remains an essential, life-saving treatment for curing childhood cancer, and there are no alternative treatments currently available. The goal of the research is not to discourage use, but to understand genetic damage so scientists can eventually develop ways to protect healthy tissues.
Why does platinum-based chemotherapy affect the liver differently?
NanoSeq analysis revealed a distinctive pattern of genetic changes exclusive to liver tissues. Researchers attribute this to the fact that the liver is the organ responsible for breaking down platinum-based chemotherapy treatments.
What are mutational signatures?
Mutational signatures are patterns of DNA damage left behind in surviving healthy cells after exposure to agents like chemotherapy. While some signatures are documented, this study used NanoSeq to reveal the massive scale of mutations accrued in children’s healthy tissues.
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