Platinum-based chemotherapy drugs cause extensive DNA damage in healthy tissues and accelerate cellular aging in pediatric cancer patients, according to a landmark study published September 10 in Science. Researchers from the Wellcome Sanger Institute, the University of Cambridge, the Francis Crick Institute, and King’s College London used advanced genomic sequencing to analyze samples from children undergoing treatment, revealing a hidden mutational impact on the liver that may explain long-term health risks survivors face decades later.
Genomic Sequencing Reveals Accelerated Cellular Aging in Pediatric Patients
According to the published study, life-saving platinum-based treatments destroy cancer cells by damaging their DNA. However, the sequencing analysis shows that surviving healthy cells accumulate mutational signatures equivalent to the genetic damage adult cells acquire over many decades. Dr Anna Wenger, first author at the Wellcome Sanger Institute and the University of Gothenburg, noted that the research reveals how certain drugs age children’s healthy tissues in a short period. The team used NanoSeq technology to analyze blood, liver tumor, and non-cancerous tissue samples from nine children. Additional samples from children receiving non-platinum treatments or no treatment at all provided a comparative baseline, according to study data.
Liver Tissue Shows Distinctive Platinum Chemotherapy Mutations
The genomic analysis uncovered a previously unseen pattern of genetic changes localized specifically within liver tissues. According to Dr Foad Rouhani, co-senior author at the Francis Crick Institute and King’s College London, the same chemotherapy drug can cause different types of DNA damage across tissues, questioning the assumption that these treatments impact all organs identically. Because platinum-based drugs are broken down in the liver, researchers suggest the organ may be particularly exposed to the processes responsible for this type of DNA damage. Some of these resulting mutations are considered cancer drivers, which may increase the risk that these cells will develop into cancer, though such severe complications remain rare among survivors.
Balancing Life-Saving Treatment with Long-Term Survivor Health
Study authors emphasize that the findings should not discourage the use of chemotherapy, which remains essential for curing childhood cancer. Instead, mapping out exact mutational signatures provides a biological explanation for premature aging symptoms reported by adult survivors. Professor Sam Behjati, co-senior author at the University of Cambridge and Director of the Cambridge Children’s Research Institute, formerly at the Wellcome Sanger Institute, stated that understanding this normal tissue damage forms the necessary first step toward developing protective treatments that reduce long-term health risks. Dr Ellie Waters-Barnes, patient advocate who was not included in this study, added that the genomic findings offer hope for future therapies that eliminate the lasting health burdens of pediatric oncology treatments.
Did You Know?
NanoSeq technology sequences both strands of DNA independently and compares results to achieve high resolution, allowing scientists to detect rare mutations in childhood tissues that conventional bulk sequencing methods can miss, according to methodology details published in Science.
Frequently Asked Questions
What causes the DNA damage in healthy cells during childhood cancer treatment?
Platinum-based chemotherapy drugs effectively destroy cancer cells by inducing DNA damage, but they also leave behind mutational signatures in surviving healthy tissues, according to researchers at the Wellcome Sanger Institute.
Why is liver tissue uniquely affected by platinum-based chemotherapy?
Scientists discovered a distinctive pattern of genetic changes in the liver that does not appear in other tissues, which researchers attribute to the breakdown of the chemotherapy treatment, which takes place in this organ.
Does this research mean children should stop receiving chemotherapy?
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