Childhood cancer treatment linked to lasting mutations in healthy tissues

Children who have received platinum-based chemotherapy carry a distinct mutational signature in their livers as a result, as well as a higher level of mutations across various healthy tissues.

Platinum-based drugs are widely used in the treatment of paediatric and adult cancers, yet they are often associated with severe long-term side effects. They act by binding to and damaging DNA, which prevents cell division and leads to the death of cancerous cells. However, they can also cause genetic damage to healthy cells, including leaving behind characteristic patterns of mutations known as mutational signatures. A study published in Science examined the genetic impact of platinum-based therapy in children treated for liver cancer.

'Our study represents a milestone in revealing the DNA damage that chemotherapy causes in normal tissues,' said first author Dr Anna Wenger from the Wellcome Sanger Institute in Hinxton, near Cambridge, and the University of Gothenburg, Sweden. 'We explored what this might mean for children who undergo this life-saving treatment at a young age, as delayed side effects from treatment often unfold over a lifetime.'

The team compared tissue samples from children who had been exposed to platinum chemotherapy with those from children who had received no such drugs, or no treatment at all. To investigate DNA damage left in healthy tissues, the research team used a highly accurate sequencing technique known as NanoSeq.

The analyses showed that platinum treatment was associated with a higher level of mutations across multiple healthy tissues. Liver cells from children treated with these drugs, for instance, had the same level of accumulated mutations found in adults due to ageing. Some of the mutations identified are known to increase the risk of developing cancer.

The researchers also uncovered a previously unknown mutational signature linked to platinum chemotherapy and unique to the liver. This may reflect the liver's role in breaking down platinum drugs, making it particularly susceptible to the resulting damage.

'As someone who is not only a recently qualified doctor but also a childhood cancer survivor, the potential impact of this research fills me with a lot of hope,' said Dr Ellie Waters-Barnes, a patient advocate who was not involved in this study. 'Hope for a future where the drugs we use to treat children with cancer do not lead to lasting health problems and secondary malignancies. Hope that children can survive cancer without feeling the burden of the treatment for the rest of their lives.'

While platinum-based chemotherapy remains essential for treating childhood cancer, the researchers emphasise that these findings could help scientists better understand its effects on healthy tissues. More research is needed to establish how these effects influence survivors' health over time, and whether it may be possible to develop strategies to reduce associated long-term health risks.