Blocking energy production pathways in an aggressive type of brain cancer in children could be a promising new therapeutic strategy, according to research in mice by Johns Hopkins Kimmel Cancer Center investigators.
The research was published March 19 in Acta Neuropathologica Communications . It provides valuable new insights about how an aggressive and hard-to-treat form of pediatric brain cancer reprograms energy production in tumor cells to support tumor growth. It also shows that using an experimental therapy to target energy production in tumor cells can slow tumor growth. These detailed molecular insights could help scientists develop a new type of metabolically targeted therapy for group 3 medulloblastoma, an often-fatal form of pediatric brain cancer.
“There is an urgent need to develop new therapies against group 3 medulloblastoma,” says senior study author Ranjan Perera, Ph.D. , director of the Center for RNA Biology at Johns Hopkins All Children’s Hospital (JHACH) in St. Petersburg, Florida. “We now have clear evidence that cancer metabolism is a potential new target.”
In 2024, Perera and his colleagues published a study in the journal Cell Reports showing that a therapy using serum oxide nanoparticles to deliver treatment to the brain shrinks group 3 medulloblastoma tumors in mice. The therapy targeted a piece of RNA called lnc-HLX-2-7 that does not encode a protein but instead binds to a section of DNA causing increased expression of the gene HLX. Increased expression of HLX encourages tumor growth by boosting expression of other tumor growth-promoting genes, accelerating cancer growth. The therapy works by blocking lnc-HLX-2-7 from binding to the DNA.
The latest study was designed to learn more details about how the nanoparticle-coated drug targeting lnc-HLX-2-7 reduces tumor growth. The experiments showed that lnc-HLX-2-7 increases oxygen consumption and energy production in the tumor cells, helping fuel explosive tumor growth. But the drug targeting lnc-HLX-2-7 reverses this, starving the tumor cells of oxygen and energy and causing them to die.
Perera and his team then tested an experimental therapy called IACS-010759 that uses small molecules to directly target oxygen use and energy metabolism in cancer cells in medulloblastoma group 3 tumors in mice. The experiments showed that IACS-010759 reduced tumor growth in the mice.
Early clinical trials already have demonstrated that targeting cellular energy production in tumor cells with IACS-010759 may effectively treat cancers of the blood, colon, breast, pancreas and prostate. Now, Perera and his team are working to develop metabolically targeted therapies specifically for this devastating form of pediatric brain cancer.
“There are a growing number of metabolically targeted therapies for other types of cancer, but this would be the first attempt to develop metabolically targeted group 3 medulloblastoma therapies,” Perera says. “There are currently no therapies for this type of cancer in part because of the challenge of delivering therapies to the brain across the blood-brain barrier. Developing small molecule therapies similar to IACS-010759 that can pass through this barrier would fill a critical need.”
Acta Neuropathologica Communications