A new study published this week in Science examined the long-term effects of platinum-based chemotherapy agents, particularly cisplatin and carboplatin, on children treated for hepatoblastoma, a rare childhood liver cancer. While these medications have dramatically improved survival rates for localized tumors from 20% to more than 80%, they work by damaging DNA and are known to cause mutations in healthy cells that could increase the risk of secondary cancers later in life.
Researchers analyzed liver tissue samples and blood from children who received platinum therapy followed by tumor removal surgery, using advanced DNA sequencing techniques called NanoSeq. They compared results to children treated with alternative drugs or no chemotherapy, as well as to fetal liver tissue. The analysis revealed that platinum exposure produced approximately 2,200 mutations per liver sample on average—a mutation burden typically observed in adult livers. This finding suggests the chemotherapy aged the liver cells of treated children, causing them to resemble adult liver tissue.
The study found a dose-dependent relationship, with children receiving both cisplatin and carboplatin showing higher mutation loads than those receiving only cisplatin. Liver cells demonstrated significantly more mutations than blood cells despite chemotherapy being a systemic treatment, indicating the liver may metabolize platinum differently or repair DNA damage differently than other tissues. Researchers identified mutations in cancer-related genes as well as genes associated with long-term changes in liver metabolism, though experts emphasized these findings do not guarantee the cells will become cancerous.
Experts called for extended survivorship monitoring of childhood liver cancer patients beyond their third decade of life. Study authors highlighted that establishing the occurrence and scope of damage enables closer clinical monitoring and earlier detection of potential complications. Looking forward, researchers suggested understanding the mechanisms behind platinum’s effects could eventually lead to development of next-generation chemotherapies that effectively treat cancer while minimizing damage to surrounding healthy tissue.
Article Attribution | Read More at Article Source
Article summary produced by Claude AI