New vulnerability discovered in aggressive childhood brain tumors

The Hopp Children's Cancer Center Heidelberg (KiTZ) is a joint institution of the German Cancer Research Center (DKFZ), Heidelberg University Hospital (UKHD), and Heidelberg University (Uni HD).

Medulloblastoma is a malignant brain tumor that primarily affects children. We now know that there are different forms of this disease. They differ, among other things, in the changes that occur in the tumor cells and in the course of the disease. The international research team has now taken a closer look at how genetic information is regulated in tumor cells. This is because it is not only changes in the genetic material itself that can play a role in the development of cancer; it is also crucial which genes a cell turns on or off.

In the process, the researchers discovered a distinctive feature in two common forms of medulloblastoma: genes that normally help immature cells mature into specialized nerve cells were strikingly less active in the tumor cells. While searching for the cause, the team came across a protein called KDM2B. This protein was particularly active in what are known as Group 4 medulloblastomas. This group is among the most common forms of medulloblastoma. The researchers suspect that KDM2B contributes to the tumor cells remaining in an immature state. When they removed the protein, genes responsible for normal cell maturation became active again.

A particularly important question was what happens when tumor cells have to function without KDM2B. In various experiments, the researchers specifically inactivated the protein. As a result, the tumor cells under study grew significantly more slowly. Tumor growth also slowed in mice, and the animals lived longer.

“To date, there are no effective targeted therapies for group 3 and 4 medulloblastomas,” says Stefan Pfister, director of the Hopp Children’s Cancer Center Heidelberg (KiTZ), head of the Department of Pediatric Neuro-Oncology at the German Cancer Research Center (DKFZ), a pediatric oncologist at Heidelberg University Hospital (UKHD), and a professor at the Heidelberg Medical Faculty of Heidelberg University. “The new findings therefore make KDM2B and the molecular processes it regulates interesting candidates for offering new treatment options in the future to children and adolescents with these brain tumors.”

In the future, therefore, researchers could investigate whether KDM2B can be specifically targeted or removed from tumor cells. However, further research is needed before this can be developed into a treatment for patients.

“Our close collaboration with Stefan Pfister began ten years ago,” says Paul Northcott, also a lead author of the study and director of the St. Jude Center of Excellence in Neuro-Oncology Sciences in Memphis, USA. “Now we not only have a better understanding of what goes wrong in gene regulation in certain subgroups of medulloblastoma, but we’ve also discovered a new potential target for future therapies.”

Stefan Pfister emphasizes that the findings represent an important first step in basic research: “The studies conducted so far have been carried out on tumor cells and mice. They point to a potential therapeutic target. However, the efficacy of a KDM2B-targeted therapy in children with medulloblastoma has yet to be demonstrated.”

 

Original publication:
Tao R., Erkek-Ozhan S., Xu B. et al.: Divergent medulloblastoma chromatin states disclose KDM2B as a selective dependency. In: Nature Genetics (online publication 24 September 2026). DOI: doi.org/10.1038/s41588-026-02745-1