Potential New Treatment Strategy Offers Hope for Hard-to-Treat Childhood Cancer

 November 30, 2025

SYDNEY — A groundbreaking discovery by Australian researchers may offer a lifeline to children battling neuroblastoma, one of the deadliest forms of childhood cancer. In a study published Friday in the journal Science Advances, a team from the Garvan Institute of Medical Research identified a new drug combination capable of bypassing the treatment resistance that makes relapsed cases so difficult to cure.

The findings, while currently in the preclinical stage, represent a significant shift in how oncologists might approach aggressive pediatric tumors, potentially allowing for more effective treatments with fewer toxic side effects.

The “Achilles’ Heel” of Current Treatments

Neuroblastoma is the most common solid tumor in children outside the brain, typically diagnosed in toddlers under two years old. While survival rates for low-risk cases are high, children with high-risk neuroblastoma face a much grimmer prognosis. According to current medical statistics, approximately 50% of high-risk patients will experience a relapse. Once the cancer returns, it becomes notoriously resistant to therapy, claiming the lives of nine out of ten young patients.

The new study, led by Associate Professor David Croucher at the Garvan Institute, sought to understand exactly why these relapsed tumors stop responding to chemotherapy.

The team discovered that many standard chemotherapy drugs rely on a specific cellular “switch”—known as the JNK pathway—to trigger cancer cell death (apoptosis). In relapsed neuroblastoma tumors, this switch is frequently broken or impaired, rendering standard treatments ineffective.

“Finding a way to overcome the resistant state of relapsed high-risk neuroblastomas has been a major goal for my lab,” said Croucher. “These tumors can be highly resistant to chemotherapy – and the statistics once patients get to that point are devastating for families.”

Bypassing the Blockage

Realizing that the front door (the JNK pathway) was locked, the researchers searched for a side entrance. They screened a library of FDA-approved drugs to identify compounds that could kill cancer cells without relying on the broken JNK switch.

They identified romidepsin, a drug currently approved for treating certain types of lymphoma. Romidepsin is a histone deacetylase (HDAC) inhibitor, a class of drugs that works by modifying how genes are expressed within a cell. Crucially, the study found that romidepsin could trigger cell death in neuroblastoma cells even when the JNK pathway was inactive.

In collaboration with the Children’s Cancer Institute, the team tested this strategy in animal models of relapsed neuroblastoma. The results were promising: adding romidepsin to standard chemotherapy regimens significantly reduced tumor growth and extended survival compared to chemotherapy alone.

“By finding drugs that don’t depend on the JNK pathway, we can still trigger cancer cell death even when this usual route is blocked,” Croucher explained.

Implications for Pediatric Health

One of the most compelling findings of the study was that the combination therapy allowed for lower doses of standard chemotherapy to achieve the same cancer-killing effect.

“This raises the possibility of reduced side effects in future treatment – an important consideration when treating young children,” the researchers noted.

Current treatments for high-risk neuroblastoma often involve “more is better” approaches—intense chemotherapy, radiation, and stem cell transplants—which can leave survivors with lifelong health issues, including hearing loss, infertility, and heart damage. A therapy that increases efficacy while potentially lowering the required dosage of toxic drugs would be a major advancement in pediatric “onco-protection.”

Expert Perspectives and Context

The medical community has long recognized the urgent need for novel approaches in treating high-risk neuroblastoma.

Dr. Hunter Jonus, a researcher specializing in high-risk neuroblastoma at Emory University (who was not involved in this specific study), has previously highlighted the severity of the landscape this new research aims to change. In commentary regarding the field’s challenges, Jonus noted that while initial treatments can be effective, “if a child’s high-risk neuroblastoma relapses after receiving chemotherapy, overall survival plummets below 20%.”

This high mortality rate is largely attributed to the “evolution” of tumor cells, which adapt to survive the initial onslaught of medication. By targeting the mechanism of this adaptation—the reliance on the JNK pathway—the Garvan Institute study offers a strategic workaround rather than just a more aggressive bombardment.

However, independent experts urge caution, noting that successful animal trials do not always translate directly to human success. The transition from “bench to bedside” requires rigorous clinical testing to ensure safety and efficacy in pediatric patients.

Limitations and Next Steps

While romidepsin is already FDA-approved for adults with lymphoma, its use in this specific combination for pediatric neuroblastoma is still experimental. The current study was conducted in laboratory settings and animal models (xenografts), not in human patients.

Associate Professor Croucher emphasized that this is a “proof of principle.” The immediate next step is to optimize the dosage schedules and delivery methods to ensure the combination is safe for young children. Since romidepsin has known safety data from its use in other cancers, the timeline for potential clinical trials could theoretically be accelerated compared to an entirely new drug.

“This represents a big step forward, but the next challenge will be working on getting these findings into the clinic,” Croucher said. “Behind every statistic is someone’s loved one… that’s what drives us every day.”

Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.

References

1. Study Citation: Hastings, J. F., et al. (2025). “Inclusion of JNK-independent drugs within multi-agent chemotherapy improves response in relapsed high-risk neuroblastoma.” Science Advances. DOI: 10.1126/sciadv.ady5599.

2. Primary Source: Garvan Institute of Medical Research. “Potential treatment to bypass resistance in deadly childhood cancer.” ecancer.org, 28 Nov 2025.