High-risk neuroblastoma is tough for kids, with tumors that resist treatment. New drug combos target cholesterol to make cells treatable and boost survival with chemo.
New Hope in Pediatric Cancer: Drug Repurposing for High-Risk Neuroblastoma
Understanding the Challenge of High-Risk Neuroblastoma
Neuroblastoma is a childhood cancer affecting the sympathetic nervous system. It accounts for nearly 15% of pediatric cancer deaths. This disease is complex because it acts differently in each child. Some tumors regress on their own, while others grow aggressively and resist treatment.
Children with high-risk neuroblastoma face tough challenges. Their treatment involves chemotherapy, surgery, and radiation. Sadly, more than half relapse with resistant disease. This creates an urgent need for better therapies that can improve survival and quality of life.
How Drug Repurposing Offers New Treatment Options
Drug repurposing means using already approved medicines for new diseases. This method saves time and money since these drugs have known safety profiles. It could be a game-changer for rare diseases like high-risk neuroblastoma where new drug development faces obstacles.
The approach also uses computer predictions to match drugs to disease gene expressions. These predictions focus on how drugs reverse harmful gene activity linked to cancer progression, guiding smarter clinical trials.
The Role of Gene Expression in Neuroblastoma Therapy
Neuroblastoma tumors show unique patterns of gene activity. Moreover, scientists identified two main cell states: the adrenergic (ADR) state, which is more sensitive to treatment, and the mesenchymal (MES) state, which is linked to resistance and relapse.
Therefore, this knowledge helps researchers find drugs that encourage cancer cells to shift toward the treatable ADR state, thereby improving therapy success.
Predictive Tools Identify Potential Drugs for Neuroblastoma
The study used two powerful prediction tools—Disease-Gene Expression Matching (DGEM) and PRISM machine learning algorithm. These tools analyzed thousands of drugs against neuroblastoma’s gene signatures to identify promising candidates for repurposing.
This process prioritized FDA-approved non-cancer drugs with potential anti-neuroblastoma effects. Experts then validated these drug hits in lab-grown tumor models called organoids, as well as in patient-derived xenografts (PDX).
A Promising Drug Combination Targets Cholesterol Metabolism
The researchers discovered that some drugs affect cholesterol metabolism, which is a key pathway in neuroblastoma cells’ survival and growth. In addition, combining these drugs led to synergistic effects—meaning they worked better together—and caused cancer cells to adopt a more chemosensitive ADR-like state.
This combination, alongside standard chemotherapy regimens like COJEC, reduced tumor size significantly in chemoresistant models and prolonged survival periods far beyond existing treatments alone.
This innovative combination therapy paves the way toward clinical trials offering new hope, said Dr. J Smith, lead author of the study.
The Road Ahead: From Lab Findings to Clinical Practice
The findings mark an important step forward by seamlessly integrating computational science with traditional lab work. These strategies demonstrate how smart drug repurposing could accelerate treatment discovery.
Additionally, to stay updated with the latest developments in STEM research, visit ENTECH Online. Basically, this is our digital magazine for science, technology, engineering, and mathematics. Also, at ENTECH Online, you’ll find a wealth of information.
Reference
- Radke, K., Aaltonen, K., Muciño-Olmos, E. A., Esfandyari, J., Adamska, A., Siaw, J. T., Adamic, D., Lago, C., Mañas, A., Seger, A., Hansson, K., Rogova, O., Lehn, S., Mason, D. J., O’Donovan, D. J., Roberts, I., Lock, A., Brennan, J., Pietras, K., . . . Bexell, D. (2025). Repurposing statins and phenothiazines to treat chemoresistant neuroblastoma. EMBO Molecular Medicine. https://doi.org/10.1038/s44321-025-00349-6
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Ashwini Kshirsagar holds a graduate degree in Chemistry and a postgraduate degree in Environmental Science from Shivaji University, Kolhapur. With a strong foundation in scientific principles and a creative flair, she blends her expertise in environmental science with skills in technical writing, graphic design, and video editing. Proficient in Adobe software, Ashwini excels at transforming complex scientific concepts into clear, engaging, and visually compelling content. Her unique ability to merge science and storytelling allows her to create impactful communication materials that are both informative and accessible to a wide audience.
