Scientists at Toronto’s The Hospital for Sick Children (SickKids) have discovered a gene that could lead to new, targeted treatments for medulloblastoma, the most common malignant brain tumor in children. In a study published in Developmental Cell, the researchers identified the KCNB2 gene as a key driver of tumor growth, opening a potential pathway for more effective therapies.
For their work, the team—which included researchers from other leading cancer centers in the United States and Canada—focused on tumor-propagating cells (TPCs), which play a central role in the development and recurrence of medulloblastoma. These cells can survive traditional cancer treatments such as chemotherapy and radiation, making them responsible for tumor metastasis. This new research discovered that the KCNB2 gene, which regulates potassium channels in cells, is essential for the growth of these tumor-propagating cells.
“Tumor-propagating cells are the main reason tumors grow and come back,” said Xi Huang, PhD, a lead author on the study and senior scientist in the developmental, stem cell & cancer biology program at SickKids. “By targeting a specific potassium channel, we were able to reduce tumor growth without impacting surrounding healthy cells,” Huang added.
Using a genetically engineered preclinical model, the investigators identified several genes associated with tumor growth and survival, two of which are involved in potassium channels—pathways that allow potassium to flow out of cells. At the same time they were screening for tumor growth-associated genes, the team also conducted an analysis of the MB transcriptome which showed that potassium channels were present at above-accepted levels in humans with the disease.
“To identify ideal therapy targets, we developed a novel in vivo screening method that shows which genes are essential to tumor survival,” said Michael Taylor, PhD, adjunct scientist at SickKids and professor at Baylor College of Medicine and Texas Children’s Cancer Center. “Our method highlighted which key blocks in a tower are necessary to keep the tower standing, which is crucial for us in trying to topple medulloblastoma.”
Investigation of the uncovered genes by the study’s first author, Jerry Fan, PhD, revealed that one of the potassium channels played a central role in aiding tumor-propagating cells to multiply, driving the growth of medulloblastoma.
“Without KCNB2, the tumor cells began to lose their integrity, triggering a chain of events that eventually interrupts the tumor propagation process and stops tumor growth,” Fan said.
The research also revealed that KCNB2 interacts with other signaling pathways, including the epidermal growth factor receptor (EGFR), which plays a role in many different cancers, and regulates cellular processes such as endocytosis and membrane tension.
This discovery offers promise for improving medulloblastoma treatment by targeting the potassium channel in tumor cells. Current treatments for the disease involve surgeries, chemotherapy, and radiation, but these options have limited effectiveness and can come with associated long-term adverse side effects due to the damage caused to cells via chemotherapy and radiation. The hope is that a new therapeutic approach targeting the KCNB2 gene could block the survival of tumor-propagating cells without harming healthy tissue.
“Identifying the molecule that can most effectively block KCNB2 is our next milestone to develop an effective targeted therapy for medulloblastoma,” Huang said.
