Platinum-based chemotherapy drugs, specifically cisplatin and carboplatin, have dramatically improved survival rates for children with hepatoblastoma, a rare childhood liver cancer, increasing five-year survival for localized tumors from 20% to more than 80%. However, these medications work by damaging DNA in cancer cells and are known to cause mutations in healthy cells, which may increase the risk of secondary cancers later in life.
A recent study published in Science examined the long-term cellular effects of platinum therapy in children treated for hepatoblastoma. Researchers collected tissue samples from the liver and blood of treated children, as well as from control groups that received different treatments or no treatment, along with fetal liver tissue. Using advanced DNA sequencing technology called NanoSeq, they analyzed the genetic damage across these samples.
The analysis revealed that platinum exposure resulted in hundreds of mutations in liver genes, with an average of 2,200 mutations per sample. This mutation burden typically appears in adult livers, suggesting that the chemotherapy accelerated the aging of liver cells in treated children. The researchers also found that mutation load increased proportionally to the amount of platinum exposure, with children receiving both cisplatin and carboplatin developing more mutations than those receiving only cisplatin. While these mutations affected cancer-related genes, they also impacted genes associated with long-term liver metabolism changes.
Liver cells showed significantly more mutations than blood cells despite chemotherapy being a systemic treatment, indicating that platinum affects different tissues differently. Researchers noted that understanding why liver cells are particularly susceptible to these effects remains unclear, though possibilities include differential drug metabolism or variations in cellular repair mechanisms. Study authors emphasized that while the findings demonstrate that damage occurs, mutations alone do not guarantee future disease development.
Experts called for long-term survivorship studies extending into patients’ third decade of life and recommended closer clinical monitoring of treated individuals. Researchers also suggested that understanding the mechanisms behind platinum’s effects could inform development of next-generation chemotherapy drugs that effectively treat cancer while minimizing damage to surrounding healthy tissue.
Article Attribution | Read More at Article Source
Article summary produced by Claude AI