Breakthrough Gene Discovery Offers New Hope for Medulloblastoma Therapy

Breakthrough Gene Discovery Offers New Hope for Medulloblastoma Therapy

Scientists at the Hospital for Sick Children (Sickkids) have identified a key gene that could lead to next-generation treatments for medulloblastoma, the most common malignant brain tumor in children.

Within cancer tumors there are special cells called tumor propagation cells that drive tumor formation and growth. Because these cells can survive standard treatments such as radiation and chemotherapy, the tumor can potentially grow back and cause a relapse.

New research results inDevelopmental cellprovides evidence for thisKCNB2Gen could improve current cancer treatments and target medulloblastoma tumor growth.

Tumor-propagating cells are the main reason why tumors grow and come back. By targeting a specific potassium channel, we were able to reduce tumor growth without affecting surrounding healthy cells. This discovery opens the door to the development of new therapies that could change the way we treat this common childhood brain cancer. “

Dr. Xi Huang, a lead author and senior scientist in the Developmental Cell Program, STEM Cell & Cancer Biology

Narrowing of tumor growth genes

Using a genetically engineered preclinical model, researchers in Dr. Michael Taylor's lab compiled a list of genes that were linked to tumor growth. Two of these genes were involved in potassium channels, which are pathways that allow potassium to flow out of cells. At the same time, analysis of the medulloblastoma transcriptome (all genes expressed by the tumor) shows that potassium channels were present above expected levels in humans.

“In order to identify ideal therapy goals, we have developed a novelIn vivoScreening method that shows which genes are essential for tumor survival “Tower stand, which is crucial for us to overthrow medulloblastoma.”

First author Dr. Jerry Fan, former Ph.D. The student in Huang's lab looked more closely at the genes and found that one of these channels plays a crucial role in the multiplication of tumor cells to promote the growth of medulloblastoma.

"WithoutKCNB2The tumor cells lost their integrity and triggered a chain of events that eventually interrupts the tumor spreading process and stops tumor growth," explains Fan.

How does potassium affect tumor growth?

Potassium is an essential ion that supports many human functions, including maintaining normal fluid levels in our cells. Imagine a water balloon – if it takes in too much water, it will burst. Scientists found blockagesKCNB2caused medulloblastoma tumor cells to swell like an overfilled balloon with water. As the cells expanded, their internal structures broke apart, stopping the mechanisms that cause tumors to grow.

Towards a new therapy for medulloblastoma

Researchers are excited about the opportunities this discovery offers for the development of medulloblastoma treatments targeting theKCNB2Gen. With support from the Sickkids Industry Partnerships & Commercialization (IP&C) Zoüros, Huang worked with a specialized Ion Channel Drug Discovery Company to evaluate the effectiveness of over 30,000 small molecules that could inhibitKCNB2Function.

Now Huang and his team are confirming the ranked molecules and will move the strongest candidates into preclinical models to test their effectiveness.

“Identifying the molecule that can block most effectivelyKCNB2“Is our next milestone in developing an effective targeted therapy for medulloblastoma,” says Huang.

This study was funded by the SONTAG Foundation, Ontario Early Investigator Award Program, Canadian Cancer Society, Cancer Research Society, Natural Sciences and Engineering Research Council (NSERC), American Brain Tumor Association, Ontario Institute for Cancer Research, Canadian Institutes of Health Research (NSERC) (NSERC CIHR), National Institutes of Health (NIH), Brainchild, Meagan's Embrace, Cancer Prevention and Research Institute of Texas (CPRIT). Michael Taylor is a CPRIT fellow in Cancer Research and Texas Children’s Cancer and Hematology Center.

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