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January 25, 2025 | Toronto, Canada
Scientists at The Hospital for Sick Children (SickKids) have made a breakthrough discovery that could lead to next-generation treatments for medulloblastoma, the most common malignant brain tumor in children. This discovery centers around a key gene, KCNB2, which could enhance current cancer treatments by targeting tumor-propagating cells that are resistant to traditional therapies like radiation and chemotherapy.
Medulloblastoma tumors contain special cells, called tumor-propagating cells, which drive tumor formation and growth. These cells can survive standard treatments, leading to tumor recurrence and relapse. Researchers have now identified KCNB2 as a promising target to combat tumor growth without harming surrounding healthy cells.
“We were able to reduce tumor growth by targeting a specific potassium channel without affecting healthy cells,” said Dr. Xi Huang, a Senior Scientist in the Developmental, Stem Cell & Cancer Biology program at SickKids and one of the lead authors of the study. “This discovery opens the door to the development of new therapies that could transform the way we treat this common childhood brain cancer.”
Discovering the Key Gene for Tumor Growth
The research team, led by Dr. Michael Taylor at SickKids, used a genetically engineered preclinical model to identify genes linked to tumor growth. Two genes related to potassium channels stood out, indicating that potassium might play a key role in supporting tumor growth. Further analysis of the medulloblastoma transcriptome revealed that these potassium channels were present in elevated levels in human tumors.
“The identification of these critical genes was achieved through a novel in vivo screening method, which helped pinpoint essential targets for tumor survival,” explained Dr. Taylor, an Adjunct Scientist at SickKids and Professor at Baylor College of Medicine and Texas Children’s Cancer Center in Texas.
How Potassium Affects Tumor Cells
Potassium, an essential ion in the body, regulates fluid levels within cells. Researchers discovered that blocking KCNB2 caused medulloblastoma tumor cells to swell with water, similar to an overfilled balloon. As the cells expanded, their internal structures broke down, preventing the growth mechanisms that lead to tumor progression.
Towards New Treatments for Medulloblastoma
The researchers are hopeful that targeting the KCNB2 gene could lead to innovative therapies for medulloblastoma. With support from the SickKids Industry Partnerships & Commercialization (IP&C) office, Dr. Huang’s team is working with a specialized ion channel drug discovery company to test over 30,000 small molecules for their ability to inhibit KCNB2. The next step is to validate the most promising candidates in preclinical models.
“Identifying the molecule that can most effectively block KCNB2 is our next milestone in developing a targeted therapy for medulloblastoma,” said Dr. Huang. “This discovery holds great potential, and we are grateful for the support from IP&C to move these findings beyond the lab and toward real-world therapies for patients.”
This study was published in Developmental Cell, with the full details available in the January 2025 issue. The research could significantly impact the future of childhood brain cancer treatments and improve outcomes for young patients.
Disclaimer: The findings of this research are in the early stages of development. Clinical applications and therapies based on these discoveries are not yet available. Further studies, including clinical trials, will be necessary before any new treatment options can be considered for patients.
More information:
Jerry J. Fan et al, “A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance,” Developmental Cell (2025), DOI: 10.1016/j.devcel.2025.01.001
