Preclinical study offers a potential new approach to the treatment of neuroblastoma and other MYC driven cancers

PHILADELPHIA, Sept. 24, 2025 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) found that combining a specialized diet with an approved medication interrupts the growth of high-risk neuroblastoma, a deadly pediatric cancer, by reprogramming tumor behavior. The findings were published in the journal Nature.

Neuroblastoma originates from primitive cells meant to form nerve tissues but that remain "undifferentiated," indicating cancer cells that haven't specialized, often suggesting a more aggressive and unfavorable prognosis. These tumors rely on a steady supply of chemicals called polyamines that are essential for rapid cell growth and tumor progression. A medicine called difluoromethylornithine (DFMO) was approved by the Food and Drug Administration (FDA) to treat children with high-risk neuroblastoma, as DFMO blocks polyamine production. However, researchers sought to improve the effectiveness of the drug by using it at high doses and combining it with a diet that is depleted of the nutrients used by the body to make polyamines (arginine). This two-step approach was anticipated to lower polyamines substantially more than low dose DFMO alone.

"Our findings show that this treatment reduced polyamines in tumors to roughly 10% of their usual levels. This reduction greatly slowed tumor growth, and in many cases, completely eliminated the tumors," said Michael D. Hogarty, MD, a lead author and an Attending Physician in the Division of Oncology at Children's Hospital of Philadelphia. "Notably, the treatment altered the way the tumor cells make proteins, making it harder for them to grow and easier for them to mature, or differentiate."

Hogarty and his team used a preclinical model to mimic MYCN-driven neuroblastoma, directly addressing the strong association between extra MYCN gene copies and aggressive neuroblastoma with poor prognosis. Animal models with tumors were divided into groups: one fed a normal diet and the other lacking amino acids for polyamine production. Each group either received DFMO in their drinking water or did not. The special diet or DFMO alone partially lowered polyamines and extended survival, but the combination had the most significant impact on tumors due to the profound polyamine depletion it caused.

The researchers plan to conduct additional preclinical studies, followed hopefully by clinical trials in children to determine the safety and efficacy of targeting this specific metabolic dependency of neuroblastoma cells. By complementing existing treatments, they hope to substantially improve patient outcomes, and because the therapy targets polyamines it may be effective in many other types of cancer that have frequent MYC gene activation.

This work was supported by the US National Institutes of Health (NIH Pioneer award (452DP1DK113643) and (R01CA163591). The work was also supported by NIH grant (R50CA211437), grants from 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. This article/publication is based upon work from COST Action Translational control in Cancer European Network (TRANSLACORE) CA21154 supported by COST (European Cooperation in Science and Technology).

Cherkaoui et al. "Reprogramming neuroblastoma by diet-enhanced polyamine depletion." Nature. Online. September 24, 2025. DOI: 10.1038/s41586-025-09564-0.

About Children's Hospital of Philadelphia: 
A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey. CHOP also operates the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia, the Behavioral Health and Crisis Center (including a 24/7 Crisis Response Center) and the Center for Advanced Behavioral Healthcare, a mental health outpatient facility. Its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit www.chop.edu.

Contact: Jennifer Lee
Children's Hospital of Philadelphia
(267) 426-6084
leej41@chop.edu

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SOURCE Children's Hospital of Philadelphia