Scientists have found that certain chemotherapy drugs can age children’s healthy cells, causing the same amount of DNA damage in a short period that would normally accumulate over decades in middle-aged adults. Results published today in Science uncover the extent of DNA damage caused by platinum-based chemotherapy in children treated for cancer.
According to the report, a previously unseen pattern of damage in the liver could help explain some of the long-term health problems experienced by survivors. Anna Wenger, PhD, postdoctoral fellow at the Wellcome Sanger Institute and the University of Gothenburg, said, “Our study represents a milestone in revealing the DNA damage that chemotherapy causes in normal tissues.”
They stress that these findings should not discourage the use of chemotherapy, which remains essential for treating childhood cancer. Instead, understanding how treatment affects healthy tissues could eventually help them develop ways to reduce health risks later in life.
Chemotherapy’s Impact on Healthy Tissues
Chemotherapy kills cancer cells by damaging their DNA as they rapidly divide. While healthy cells can survive this damage, the treatment can leave mutational signatures with unknown effects on the long-term health of survivors. To understand these changes, Wenger’s team used a genomic sequencing method developed at the Wellcome Sanger institute known as nanorate sequencing (NanoSeq).
This technique is especially useful when sequencing childhood tumors, as these have fewer shared mutations with healthy tissues that can be missed by conventional bulk sequencing methods. The team analyzed 186 samples covering a wide range of tissues from nine children with liver cancer, collected after treatment with platinum-based chemotherapy.
Findings and Implications
The analysis revealed substantially more DNA changes in healthy cells following platinum-based chemotherapy, with some children showing levels of genetic damage comparable to those found in adult tissues. Some of these mutations are considered cancer drivers, meaning they can potentially contribute to the development of cancer.
Importantly, results unveiled a distinctive pattern of DNA damage in liver tissue that had not previously been observed. The signature was not found in other tissues and appeared to be specifically associated with platinum-based chemotherapy. Because platinum-based drugs are broken down in the liver, the organ may be particularly exposed to the processes responsible for this type of DNA damage.
Foad J. Rouhani, MD, PhD, group leader at the Francis Crick Institute and honorary consultant transplant surgeon at King’s College Hospital, said, “Our findings have unearthed something quite unprecedented about chemotherapy and DNA damage: The same chemotherapy drug can cause different types of DNA damage across tissues.”
The observation that the same chemotherapy drug can cause different types of DNA damage across tissues is significant, as it challenges the assumption that chemotherapy causes uniform DNA damage in all tissues. This discovery may have important implications for the development of targeted therapies to mitigate the effects of chemotherapy on healthy tissues.
Future Research Directions
The findings may partly explain why childhood cancer survivors commonly face health issues related to premature aging. However, further research will be needed to understand exactly how these mutations affect the long-term health of survivors and whether the damage can be prevented or reduced. Sam Behjati, MD, PhD, head of pediatrics at the University of Cambridge and director of the Cambridge Children’s Research Institute, said, “Chemotherapy is the key to curing cancer in children, and there is no alternative.”
Behjati added, “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 them to develop protective treatments to reduce long-term health risks for childhood cancer survivors.”
It is a fact that chemotherapy is essential for treating childhood cancer.
As they continue to explore the effects of chemotherapy on healthy tissues, they may uncover new ways to mitigate the risks associated with this life-saving treatment. In the meantime, the findings of this study serve as a reminder of the complexities and challenges involved in treating childhood cancer.
The research team will continue their work to understand the effects of chemotherapy on healthy tissues.
Further studies will be necessary to fully elucidate the relationship between platinum-based chemotherapy and the distinctive pattern of DNA damage observed in liver tissue. Additionally, researchers will need to investigate whether similar patterns of DNA damage occur in other tissues and organs, and how these changes impact the long-term health of childhood cancer survivors.
