Chemotherapy Ages Children’s Healthy Cells, Study Finds

A team led by researchers at Wellcome Sanger Institute has identified the extent of DNA damage caused by platinum-based chemotherapy in childhood cancer patients, along with a previously hidden effect on the liver, opening the door to future research on ways to limit this damage.

Published in Science, the study found that while chemotherapy destroys cancer cells effectively, it can “age” a child’s healthy cells, leaving them with roughly the same number of DNA changes that adult cells normally build up over decades. This offers a plausible biological explanation for why childhood cancer survivors often develop health problems later in life, including secondary cancers and liver disease.

The goal of the research is not to discourage chemotherapy, which remains essential to curing childhood cancer. Instead, by identifying exactly how these drugs damage healthy tissue at the genetic level, the scientists hope to eventually find ways to prevent or reduce that damage and lower long-term health risks for survivors. As co-senior author Sam Behjati put it: “Chemotherapy is the key to curing cancer in children, and there is no alternative. At the same time, chemotherapy causes damage to normal tissues which can manifest as adverse effects in later life. Our work now reveals a plausible mechanism, DNA damage in normal tissues, through which chemotherapy in childhood may cause late adverse effects. The next step will be to gain a deeper understanding of this damage which may enable us to develop protective treatments to reduce long-term health risks for childhood cancer survivors.”

Chemotherapy generally works by damaging DNA in cancer cells until they die, a process that can also leave surviving healthy cells with patterns of DNA damage known as mutational signatures. Some of these signatures have been documented before, but their impact on health has not always been clear.

Using a new sequencing technique called NanoSeq2, the team analyzed 186 blood, liver tumor, and non-cancerous liver tissue samples from nine children treated with platinum-based chemotherapy, alongside comparison samples from children who received non-platinum treatment or no chemotherapy at all.

The analysis showed a much higher number of DNA changes across multiple tissues after platinum-based treatment, with some children carrying as many genetic changes as are normally seen in adult tissue. Some of these changes are considered cancer drivers, which may raise the risk that affected cells will develop into cancer, though this remains a very rare complication. The study also revealed a previously unseen pattern of genetic changes found only in liver tissue and linked to platinum-based chemotherapy; because it appeared solely in that organ, the team suggests it may arise as the liver breaks down the drug.