Childhood Chemotherapy Drugs Leave Liver Cells With Mutations Like an Adult's, Study Finds

Platinum-based chemotherapy drugs cisplatin and carboplatin are a lifeline for children with certain cancers, including hepatoblastoma, a rare childhood liver cancer. The drugs transformed hepatoblastoma's five-year survival rate from 20% to more than 80% for localized tumors. But platinum drugs damage DNA, causing mutations in healthy cells too, potentially raising the risk of new cancers later in life. This has been documented in adults, but the picture is less clear in children.

A study published Thursday in the journal Science, co-authored by Foad Rouhani, a professor at King's College London, examined children who received platinum therapy for hepatoblastoma before surgery to remove the tumor. The team sampled healthy and cancerous liver tissue, plus blood, analyzing them with a DNA-sequencing technique called NanoSeq. They compared the results with children treated with other drugs, untreated children, and fetal liver tissue.

Platinum exposure led to hundreds of mutations in genes — on average 2,200 per liver sample — a mutation burden usually found in adult livers, meaning the drugs aged the children's liver cells. Mutation load rose with platinum exposure: children who received only cisplatin had fewer mutations than those who received both cisplatin and carboplatin. The authors said these mutations could raise the likelihood of liver disease or secondary tumors.

Liver cells carried far more mutations than blood cells, even though chemotherapy is a systemic treatment. “The platinum is doing something differently to liver cells than other cells,” said Rouhani, adding it is unclear whether the drug is metabolized differently there or liver cells repair differently. He cautioned the mutations do not mean the cells will definitely turn cancerous — only that there is potential for problems later.

In a perspective article, Baylor College of Medicine professors Sanjeev Vasudevan and Donald Williams Parsons wrote that the findings “provide strong evidence for conducting survivorship studies of children that have undergone treatment for liver cancer beyond their third decade of life.”