Australian researchers at the Garvan Institute of Medical Research in Sydney have identified a potential new treatment approach for children with neuroblastoma, a cancer that often returns after initial therapy. The study, published in Science Advances, demonstrates that combining an existing cancer drug with standard chemotherapy may help overcome the resistance that develops in relapsed neuroblastoma cases.
Neuroblastoma is the most common solid tumor found in children outside the brain and typically affects those under two years old. While outcomes are good for low-risk patients, about half of all cases are classified as high-risk due to aggressive tumors that have already spread. Among these high-risk patients, 15 percent do not respond to initial treatment, and half of those who do respond experience a recurrence.
The research team led by Associate Professor David Croucher examined why neuroblastoma becomes resistant to therapy. By comparing lab-grown cells and tumor samples from children at diagnosis and after relapse, they discovered that many chemotherapy drugs depend on the JNK pathway—a cellular mechanism that triggers cell death. In relapsed tumors, this pathway often fails, making treatments less effective.
To find alternatives, the team screened FDA-approved drugs with pediatric safety data for their ability to kill neuroblastoma cells without relying on the JNK pathway. They identified romidepsin—currently used for certain lymphomas—as particularly effective regardless of whether the JNK pathway was functional.
Collaborating with the Children's Cancer Institute, researchers tested romidepsin combined with standard chemotherapy in animal models of relapsed neuroblastoma. The combination reduced tumor growth and extended survival compared to chemotherapy alone. Notably, lower doses of chemotherapy paired with romidepsin achieved similar results as higher doses used alone, suggesting a possibility for fewer side effects in future treatments.
Associate Professor Croucher noted that while these findings represent progress, further research is needed before clinical application can begin. "This represents a big step forward, but the next challenge will be working on getting these findings into the clinic," he said. "We're using this data as proof of principle to develop the best ways to deliver these treatments."
Romidepsin's existing approval for other cancers and its previous safety testing in children could speed up its development as a treatment option for neuroblastoma. However, additional studies and clinical trials are required to confirm its safety and effectiveness for this specific use.
"Behind every statistic is someone's loved one," said Associate Professor Croucher. "Understanding these molecular mechanisms gives us hope we can develop more effective treatments for patients and their families who currently face limited options – and that's what drives us every day."
