Australian researchers have identified a promising new approach to treating neuroblastoma, a rare and often aggressive cancer primarily affecting young children [[1]]. Published in *Science Advances*,the study details a drug combination that appears to overcome resistance mechanisms developed by the tumors,offering renewed hope for patients who relapse – a challenge faced by as many as 90% of those initially responding to treatment. The findings center on repurposing an existing drug, romidepsin, to attack cancer cells through an alternate pathway, possibly reducing both tumor growth and the harsh side effects of conventional chemotherapy [[2]].
A new discovery by Australian researchers offers potential for improved treatment of neuroblastoma, an aggressive cancer that currently sees a high rate of relapse – affecting nine out of ten young patients whose cancer returns. The research team at the Garvan Institute of Medical Research in Sydney identified a drug combination capable of bypassing the defense mechanisms developed by these tumors, potentially preventing recurrence.
The findings, published today in Science Advances, demonstrate that a drug already approved for other cancers can trigger the death of neuroblastoma cells through alternative pathways when standard treatment routes are blocked. This breakthrough could lead to more effective therapies for children whose cancers no longer respond to conventional chemotherapy. Neuroblastoma is a particularly challenging cancer to treat, and new approaches are urgently needed.
Neuroblastoma is the most common solid tumor in children outside of the brain. It develops from nerve cells located in the adrenal glands above the kidneys, or along the spine, chest, abdomen, or pelvis. It is typically diagnosed in children under the age of two. While children with low-risk disease generally have excellent outcomes, approximately half of patients are diagnosed with high-risk neuroblastoma – an aggressive form where the tumor has already spread. Of these high-risk patients, 15 percent do not respond to initial treatment, and half of those who initially respond experience a relapse.
Why Treatments Stop Working
Researchers initially investigated why neuroblastoma becomes resistant to treatment. They studied neuroblastoma cells grown in the lab and compared tumor samples from the same children taken at the time of diagnosis and after their cancer returned. This allowed them to track the changes that occur as the cancer develops resistance.
They discovered that many standard chemotherapy drugs rely on the same cellular “switch,” known as the JNK pathway, to trigger the death of cancer cells. In relapsed tumors, this switch often stops functioning, rendering treatments ineffective.
Finding a way to overcome the resistance of high-risk, relapsed neuroblastomas has been a major goal of my lab. These tumors can be very resistant to chemotherapy – and the statistics once patients reach this point are devastating for families. By finding drugs that don’t rely on the JNK pathway, we can still trigger cancer cell death even when that usual pathway is blocked.”
Professor David Croucher, Garvan Institute of Medical Research
A Promising Drug Emerges
Seeking treatments that don’t depend on this cellular switch to induce cell death, the team screened a large collection of FDA-approved drugs with available pediatric safety data, looking for candidates that could be quickly adopted for clinical use. They identified romidepsin, a drug currently used to treat certain lymphomas, as particularly effective against neuroblastoma cells, regardless of whether the JNK pathway was functioning.
In collaboration with the Children’s Cancer Institute, the team used animal models of relapsed neuroblastoma to test whether adding romidepsin to standard chemotherapy could overcome resistance.
In their models, they found that the new combination reduced tumor growth and extended survival compared to standard treatment alone, indicating reduced resistance. Furthermore, when combined with romidepsin, lower doses of standard chemotherapy produced the same anti-cancer effect as higher doses of chemotherapy alone. This raises the possibility of reducing side effects in future treatment – an important consideration when treating young children.
Next Steps: Toward Clinical Application
While the lab results are encouraging, Professor Croucher emphasizes that further research is needed before these findings can be translated into patient care. His team is now focused on optimizing combined treatment schedules and delivery methods to ensure safety and efficacy.
“This represents a significant step forward, but the next challenge will be to translate these findings into the clinic,” Professor Croucher explained. “We are using this data as proof of principle to develop the best ways to deliver these treatments.”
Romidepsin is already approved for use in other cancers and has been tested for safety in children, which could potentially accelerate the development of the drug as a new treatment option for neuroblastoma. However, any clinical application will require further testing and clinical trials to establish the safety and efficacy of the combination in treating neuroblastoma.
“Behind every statistic is a loved one,” Professor Croucher said. “Understanding these molecular mechanisms gives us hope that we can develop more effective treatments for patients and their families who are currently facing limited options – and that’s what motivates us every day.”
