Bromodomain-protein inhibition significantly extends survival of DIPG xenograft model.
Northwestern Medicine scientists have found a molecule that stops the growth of an aggressive pediatric brain tumor. Every year, about 300 children < 10 years old in the U.S. develop a diffuse intrinsic pontine glioma (DIPG). “This tumor kills every single kid who gets DIPG within 1 year. No one survives,” said Andrea Piunti, a postdoctoral fellow in Shilatifard’s lab in biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine. Radiation therapy only prolongs patients’ survival by a few months, he noted.
Shilatifard’s lab previously identified the pathway via which a mutation causes cancer in studies with fruit flies, which was published in Science a few years ago. He and colleagues believed the pathway would be a good target to thwart the tumor and pushed forward with their molecular studies. In a study with Hashizume’s group, they demonstrated mice in the experiment, which had the drug delivered through their abdomen, had an increased survival of 20 days, which is a long time in the life of a mouse, Piunti said. Now the team at Northwestern Medicine and Lurie Children’s is working on delivering the drug to the brain stem to see if the effect will be more potent and effective.
To test the molecule, scientists took tumor cell lines from a pediatric patient that was untreated and injected those cells into the brain stem of a mouse. The human tumor engrafted in the brain of the mouse. The mouse was then treated with the molecule while scientists monitored the tumor. The molecule stopped the growth of the tumor cells and forced them to differentiate into other cells, thereby halting its growth.
This molecule detaches bromodomain proteins, from their binding to a mutant protein, the histone H3K27M, which is present in more than 80% of these tumors. While the molecule itself is not yet available commercially, another similar class of molecules, BET inhibitors, is being tested in clinical trials for pediatric leukemia and other types of tumors. These could be used in a clinical trial for the pediatric tumor, Piunti said.
https://news.northwestern.edu/stories/2017/february/molecule-stops-fatal-pediatric-brain-tumor/
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