Promising Treatment Strategy can Fight Deadly Brain Tumor in Children

New study finds that an inhibitor of an enzyme known as ACVR1 slows tumor growth and extends survival in an animal model of diffuse intrinsic pontine glioma (DIPG), a fatal brain tumor in kids. The findings of the study are published in the journal Nature Communications. "Our results are encouraging and suggest that it might be reasonable to test an inhibitor of this enzyme in a clinical trial," says senior author Oren Becher, MD, from Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago and Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine. "Before that, we need to evaluate different ACVR1 inhibitors in animal models to make sure we bring the safest and effective agent to trials with children."

In 2014, Dr. Becher's lab co-discovered that ACVR1 mutations are found in approximately 25 percent of DIPGs, leading the enzyme to be overactive.

In the current study, Dr. Becher and colleagues demonstrate for the first time in an animal model that this enzyme mutation cooperates with a histone mutation (H3.1 K27M) found in 20 percent of DIPGs. Together, these mutations are important in initiating tumor development.

Histone is a protein that acts as a spool for DNA, helping to package the six-foot-long DNA strand into the tiny nucleus of every cell. Histones also help regulate which genes turn on and off, a process that goes awry when there is a histone mutation.

"Our future work will examine why and how the ACVR1 and histone mutations work together to trigger DIPG development," says Dr. Becher, who also is the Rory David Deutsch Malignant Brain Tumor Research Scholar. "Greater insight into this process will bring us closer to identifying a successful therapy for children with DIPG."

Source-Eurekalert