Childhood chemo leaves aging marks on the liver

Platinum-based chemotherapy drugs such as cisplatin and carboplatin have transformed survival rates for children with hepatoblastoma, a rare liver cancer. Five-year survival rose from around 20% to more than 80% for localised tumours. But these drugs work by damaging DNA, including in healthy cells. The study, published in Science, now maps the extent of that damage in the livers of children treated for hepatoblastoma.

The researchers analysed liver cells from children who had received cisplatin or carboplatin. They identified extensive and specific mutation patterns in the DNA, a kind of molecular fingerprint left by the chemotherapy. These patterns partly resemble the somatic mutation signatures seen in normal liver ageing, but appearing earlier and in larger numbers than would be expected.

Long-term cancer risk

Somatic mutations are DNA changes in body cells that accumulate gradually over a lifetime. The findings suggest that children who receive platinum chemotherapy may start adult life with a much higher mutation burden in their liver. The researchers cautiously note this could, over the long term, raise the risk of secondary tumours. Whether and to what degree that risk materialises remains unclear from this study alone.

Balancing benefit and risk

From a longevity perspective, this is a striking finding: a life-saving cancer treatment may accelerate the biological age of an organ. This does not change current treatment recommendations, since the alternatives are often worse. But it underlines why long-term follow-up of childhood cancer survivors is so important. These findings are preliminary and apply specifically to the patient group studied.

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