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PHILADELPHIA, Sept. 24, 2025 ~ A recent study conducted by researchers at Children's Hospital of Philadelphia (CHOP) has found a promising new treatment for high-risk neuroblastoma, a deadly pediatric cancer. The study, published in the journal Nature, shows that combining a specialized diet with an approved medication can effectively interrupt the growth of this aggressive cancer by reprogramming tumor behavior.

Neuroblastoma is a type of cancer that originates from primitive cells meant to form nerve tissues. However, these cells remain "undifferentiated," meaning they have not specialized and often lead to a more aggressive and unfavorable prognosis. These tumors rely on a steady supply of chemicals called polyamines, which are essential for rapid cell growth and tumor progression.

The medication used in this study, difluoromethylornithine (DFMO), was approved by the Food and Drug Administration (FDA) to treat children with high-risk neuroblastoma. DFMO works by blocking polyamine production in the body. However, researchers at CHOP wanted to improve the effectiveness of the drug by using it at higher doses and combining it with a specialized diet that depletes the nutrients needed for polyamine production.

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"Our findings show that this two-step approach greatly reduced polyamines in tumors to only 10% of their usual levels," said Dr. Michael D. Hogarty, an Attending Physician in the Division of Oncology at CHOP and lead author of the study. "This reduction significantly slowed tumor growth and, in many cases, completely eliminated the tumors."

The combination treatment not only lowered polyamines but also altered how tumor cells make proteins. This change made it harder for them to grow and easier for them to mature or differentiate.

To test their findings, Hogarty and his team used a preclinical model that mimicked MYCN-driven neuroblastoma. This type of neuroblastoma is known for its aggressive nature and poor prognosis due to extra copies of the MYCN gene. The animal models with tumors were divided into groups, with one group receiving a normal diet and the other lacking amino acids needed for polyamine production. Each group was also given either DFMO in their drinking water or no treatment at all.

The results showed that the combination of the specialized diet and high-dose DFMO had the most significant impact on tumors due to the profound depletion of polyamines it caused. The researchers now plan to conduct further preclinical studies and, hopefully, clinical trials in children to determine the safety and efficacy of this treatment.

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This study was supported by grants from the US National Institutes of Health (NIH), including a Pioneer award (452DP1DK113643) and R01CA163591. It was also supported by grants from various foundations, including the NOMIS Foundation, Holcim-Stiftung Wissen, Gertrud-Hagmann-Stiftung für Malignom-Forschung, EMDO-Stiftung, and Heidi Ras Grant of the FZK University Children's Hospital Zürich. Additionally, this work was based on research from COST Action Translational control in Cancer European Network (TRANSLACORE) CA21154 supported by COST (European Cooperation in Science and Technology).

The researchers hope that by targeting this specific metabolic dependency of neuroblastoma cells, they can complement existing treatments and substantially improve patient outcomes. Furthermore, because this therapy targets polyamines, it may also be effective in treating other types of cancer with frequent MYC gene activation.

This groundbreaking study provides new hope for children battling high-risk neuroblastoma and paves the way for future research in this area. The article "Reprogramming neuroblastoma by diet-enhanced polyamine depletion" can be found online in Nature on September 24th, 2025 with DOI: 10.1038/s41586-025-09564-0.

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