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Chemotherapy speeds up DNA-level aging

Chemotherapy leads to faster aging at the DNA level of healthy cells in children with cancer, new research shows. This aging contributes to the increased risk of developing a new, second cancer in childhood cancer survivors. PhD candidate Eline Bertrums: ‘Our research lays the foundation for examining if a different treatment could reduce or even prevent the risk of a second cancer.’

Chemotherapy is an important part of treatment for children with cancer, and is helping increasing numbers of children to be cured. Childhood cancer survivors do sometimes experience late effects from their treatment, including a higher risk of developing a second cancer. That risk is very small, but about five to six times greater than in the ‘normal’ population. Ten years after treatment, survivors’ risk has returned to normal, low levels.

Blood stem cells

In new research, published in the journal Cancer Discovery, researchers from the Van Boxtel group at the Princess Máxima Center compared the healthy blood stem cells of 24 children before and after their chemotherapy treatment. They found that the natural aging processes in the healthy cells had sped up: the blood stem cells of children after the treatment contained a notably higher number of changes in the DNA compared to the blood stem cells of the same children before the treatment.

Harmful effects

Dr. Ruben van Boxtel, research group leader at the Princess Máxima Center and Oncode Investigator, is leader of the new study. He says: ‘We found that accelerated DNA aging turned out to be the main cause of the harmful side effects of chemotherapy treatment. Our research also showed that particular forms of chemotherapy, with platinum or thiopurine, caused DNA damage that can directly lead to the development of a second cancer.

‘Even though our results may sound worrying, the therapy still does much less damage than the leukemia a child is being treated for,’ emphasizes Van Boxtel. ‘The vast majority of children do not develop a second cancer after treatment for leukemia. That is why it is important in the future to find out which children do have that increased risk.’

Lowering or even preventing risk

The findings from the new study will help researchers determine the most harmful forms of chemotherapy, and could help develop less harmful treatments in the future. The results are known to pediatric oncologists, who choose the best therapy for a child by weighing the benefit against the possible side effects and late effects.

PhD students Eline Bertrums, Axel Rosendahl Huber and Jurrian de Kanter in the Van Boxtel group worked together on the research. ‘In our new study, we show the effects of certain leukemia therapies on DNA,’ says Bertrums. ‘With this, we hope to be able to predict which children have a greater risk of developing a second cancer. The next step is to investigate if we can pick them out sooner. Our research lays the foundation for examining whether a different treatment can lower or even prevent the risk of a second cancer.’

Risk decreases again

It looks like the accelerated aging decreases with time. The researchers found fewer signs of aging in the blood stem cells that had been sampled the longest after treatment. More research is needed to find out why this is the case, but this finding seems consistent with previous research showing that the risk of a second cancer diagnosis ten years after treatment is back at the level of children who have not had cancer.

Are you or is your child under treatment for leukemia and do you have any questions about this research? Please read the Frequently Asked Questions page or contact your attending physician.