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Blocking Fructose Metabolism Boosts Immune Response to Childhood Cancer

Researchers at Johns Hopkins may have found a new approach to group 3 medulloblastoma, a deadly and hard-to-treat pediatric brain cancer. Mouse experiments suggest that disrupting how tumor cells generate energy can slow the disease. The research was conducted at the Kimmel Cancer Center and published in Acta Neuropathologica Communications. 

Group 3 medulloblastoma is one of the most difficult pediatric brain cancers to treat, and effective therapies remain scarce. The new research reveals how tumor cells rewire their energy production to fuel rapid growth. It also shows that interfering with those processes can slow the disease. 

Senior author Ranjan Perera, Ph.D., of Johns Hopkins All Children’s Hospital, said the work points toward a largely unexplored therapeutic avenue. According to the researcher, there is a critical need for alternative group 3 medulloblastoma therapies, and the team’s findings have opened up a potential treatment pathway by targeting cancer metabolism. 

The study builds on earlier work published in Cell Reports in 2024. That research showed nanoparticle-based therapy could reduce group 3 medulloblastoma tumors in mice. At its core was a non-coding RNA molecule called lnc-HLX-2-7. Carrying no protein instructions, it instead latches onto a stretch of DNA, prompting the gene HLX to become more active. Elevated HLX activity amplifies other genes that drive tumor growth, accelerating cancer progression. It worked by blocking lnc-HLX-2-7 from attaching to the DNA. 

This latest study set out to understand in greater detail how the lnc-HLX-2-7 drug reduces tumor growth at the cellular level. Experiments revealed that lnc-HLX-2-7 ramps up oxygen consumption and energy output in tumor cells, sustaining their rapid proliferation. When the drug was applied, it reversed this effect. It cut off the tumor cells’ oxygen and energy supply, triggering cell death. 

IACS-010759, a small-molecule compound that interferes with how cancer cells consume oxygen and produce energy, was also tested. In mouse models of group 3 medulloblastoma, IACS-010759 reduced tumor growth. Early clinical trials have shown the compound is active against blood, colon, breast, pancreatic, and prostate cancers. 

It has not previously been tested for this pediatric brain tumor. The compound is one of several experimental agents targeting cancer cell metabolism, a field that has gained traction across multiple tumor types. 

The team is now working to develop metabolically targeted therapies specifically for group 3 medulloblastoma. A central challenge is the blood-brain barrier, which limits what substances can enter the brain. Crossing it has long complicated drug delivery for brain tumors. 

Perera noted that the lack of approved treatments makes the disease especially devastating for patients and families. He believes the development of small-molecule therapies such as IACS-010759 that can bypass the blood-brain barrier will be key to developing more effective glioblastoma treatments. 

With for-profit firms like CNS Pharmaceuticals Inc. (NASDAQ: CNSP) also focused on developing the next generation of treatments indicated for glioblastoma and other pediatric central nervous system cancers, there is hope that these diseases could soon be treatable for the thousands diagnosed with these malignancies. 

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Alex Pearon

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Alex Pearon

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