Blocking Fructose Metabolism Boosts Immune Response to Childhood Cancer, Johns Hopkins Study Finds

Researchers at Johns Hopkins Medicine have identified a potential new strategy for treating group 3 medulloblastoma, a particularly aggressive and difficult-to-treat form of childhood brain cancer. In a study published in Acta Neuropathologica Communications, the team found that blocking fructose metabolism in tumor cells can slow disease progression and boost the immune system's ability to fight the cancer.

Medulloblastoma is the most common malignant brain tumor in children, and group 3 subtype has the poorest prognosis, with a five-year survival rate of only about 50%. Current treatments, including surgery, radiation, and chemotherapy, often cause long-term side effects, highlighting the need for more targeted therapies.

The Johns Hopkins team, based at the Kimmel Cancer Center, conducted experiments in mouse models of group 3 medulloblastoma. They discovered that these cancer cells rely heavily on fructose, a type of sugar, for energy. By inhibiting an enzyme called ketohexokinase (KHK), which is involved in fructose metabolism, the researchers were able to reduce tumor growth and increase the infiltration of immune cells, particularly CD8+ T cells, into the tumors.

“Our findings suggest that targeting fructose metabolism could be a promising approach to enhance the immune response against group 3 medulloblastoma,” said Dr. Eric Raabe, a pediatric oncologist and senior author of the study. “This could potentially lead to new treatments that are more effective and less toxic than current therapies.”

The study also highlighted the role of the tumor microenvironment in suppressing immune responses. By blocking fructose metabolism, the researchers found that the tumors became more susceptible to attack by the immune system. This dual effect—starving the cancer cells of energy and reactivating the immune response—could be a key to improving outcomes for patients.

While the research is still in preclinical stages, it opens the door for clinical trials of drugs that inhibit fructose metabolism, such as those being developed for other cancers. For-profit companies like CNS Pharmaceuticals Inc. (NASDAQ: CNSP) are also focused on developing next-generation treatments for glioblastoma and other brain cancers, though their approaches may differ.

The Johns Hopkins study adds to a growing body of evidence that metabolic reprogramming is a hallmark of cancer and that targeting specific metabolic pathways can be an effective therapeutic strategy. Further research will be needed to determine the safety and efficacy of this approach in human patients.

For more information on the study, visit the Kimmel Cancer Center's website at https://www.hopkinsmedicine.org/kimmel-cancer-center.