Home · Health · Sep 10 archive
Platinum-Based Chemotherapy Ages Children’s Liver Cells, Study Shows
Confirmed
In Short: A new study reveals that platinum-based chemotherapy in children causes extensive DNA mutations in liver cells, similar to those found in adult livers, potentially increasing the risk of liver pathologies.
Researchers from King’s College in London and other institutions have found that platinum-based chemotherapy, a critical treatment for childhood cancers, causes hundreds of mutations in liver cells, making them resemble adult liver cells. According to Foad Rouhani, a professor at King’s College, the mutations could lead to long-term changes in liver metabolism and increase the risk of liver pathologies or secondary tumors. The study, published in the journal Science, compared liver tissues from children treated with platinum-based chemotherapy to those from children treated with other drugs or not treated at all, as well as fetal liver tissue. The analysis revealed a distinctive pattern of DNA damage in liver tissue that was not observed in other tissues and was specifically associated with platinum-based chemotherapy.
The mutations were found to be more prevalent in liver cells than in blood cells, even though chemotherapy is a systemic treatment. Rouhani noted that the platinum agents may be metabolized or repaired differently in liver cells compared to other cells, though the exact mechanism remains unclear. The study also found that the mutation load increased proportionally to the exposure to platinum-based chemotherapy, with children who received both cisplatin and carboplatin showing a higher number of mutations than those who received only cisplatin.
Platinum-based chemotherapy, such as cisplatin and carboplatin, has significantly improved the prognosis for hepatoblastoma, a rare cancer of the liver that is the most commonly diagnosed in childhood. The five-year survival rate for localized tumors has risen from 20% to more than 80%. However, these medications, while effective, also cause DNA damage in healthy cells, potentially raising the risk of new cancers later in life. The mutations have been documented in adults, but the impact on children is less clear.
Scientists are exploring alternative approaches to mitigate the side effects of chemotherapy. A study published in the journal Science suggests that administering psilocybin, the hallucinogenic compound found in magic mushrooms, before chemotherapy might prevent chemotherapy-induced peripheral neuropathy, a condition that affects about two-thirds of patients who receive chemo. The study by a team of doctors and researchers at the University of Texas MD Anderson Cancer Center found that lab mice given psilocybin before receiving chemotherapy were shielded from nerve damage.
What's confirmed
- Researchers from King’s College in London and other institutions have found that platinum-based chemotherapy, a critical treatment for childhood cancers, causes hundreds of mutations in liver cells, making them resemble adult liver cells. According to Foad Rouhani, a professor at King’s College, the mutations could lead to long-term changes in liver metabolism and increase the risk of liver pathologies or secondary tumors. The study, published in the journal Science, compared liver tissues from children treated with platinum-based chemotherapy to those from children treated with other drugs or not treated at all, as well as fetal liver tissue. The analysis revealed a distinctive pattern of DNA damage in liver tissue that was not observed in other tissues and was specifically associated with platinum-based chemotherapy.
- The mutations were found to be more prevalent in liver cells than in blood cells, even though chemotherapy is a systemic treatment. Rouhani noted that the platinum agents may be metabolized or repaired differently in liver cells compared to other cells, though the exact mechanism remains unclear. The study also found that the mutation load increased proportionally to the exposure to platinum-based chemotherapy, with children who received both cisplatin and carboplatin showing a higher number of mutations than those who received only cisplatin.
- Platinum-based chemotherapy, such as cisplatin and carboplatin, has significantly improved the prognosis for hepatoblastoma, a rare cancer of the liver that is the most commonly diagnosed in childhood. The five-year survival rate for localized tumors has risen from 20% to more than 80%. However, these medications, while effective, also cause DNA damage in healthy cells, potentially raising the risk of new cancers later in life. The mutations have been documented in adults, but the impact on children is less clear.
- Scientists are exploring alternative approaches to mitigate the side effects of chemotherapy. A study published in the journal Science suggests that administering psilocybin, the hallucinogenic compound found in magic mushrooms, before chemotherapy might prevent chemotherapy-induced peripheral neuropathy, a condition that affects about two-thirds of patients who receive chemo. The study by a team of doctors and researchers at the University of Texas MD Anderson Cancer Center found that lab mice given psilocybin before receiving chemotherapy were shielded from nerve damage.
What's still developing
- The researchers sampled tissues from the liver — both healthy and cancerous — and the patient’s blood, analyzing them through a sophisticated DNA sequencing technique called NanoSeq.
- Results published today in Science uncover the extent of DNA damage caused by platinum-based chemotherapy in children treated for cancer, including a previously unseen pattern of damage in the liver that could help explain some of the long-term health problems experienced by survivors.
- “Our study represents a milestone in revealing the DNA damage that chemotherapy causes in normal tissues,” said Anna Wenger, PhD, postdoctoral fellow at the Wellcome Sanger Institute and the University of Gothenburg.
- “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,” said Foad J.
- “Chemotherapy is the key to curing cancer in children, and there is no alternative,” said Sam Behjati, MD, PhD, head of pediatrics at the University of Cambridge and director of the Cambridge Children’s Research Institute.
- “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 researchers stress that these findings should not discourage the use of chemotherapy, which remains essential for treating childhood cancer.
- Chemotherapy kills cancer cells by damaging their DNA as they rapidly divide.
- The 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.