The samples, taken from 16 affected children from the U.S. and Europe, were used in the search for a therapy that could kill or stop the growth of DIPG cells. After just six years, researchers found that panobinostat and similar gene-regulating drugs may be successful at inhibiting DIPG cell growth and extending patient survival rates.
The study, which was partially funded by the NIH, Department of Defense, and over 25 nonprofits, was published in Nature Medicine.
“It’s astounding. In only six years, scientists have gone from knowing virtually nothing about this tumor to understanding its underlying genetics and finding a potential therapy,” said Jane Fountain, PhD, program director at the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH. “This study epitomizes collaborative medicine at work. It took a dedicated team of international scientists working with patients, families and foundations to get to this point.”
Researchers used high-throughput screening to rapidly search for effective compounds, simultaneously testing 83 known or potential cancer drugs on the DIPG cells. They found that histone deacetylase (HDAC) inhibitors slowed DIPG cell growth, focusing on panobinostat, which is designed to block multiple types of histone deacetylases. Panobinostat successfully inhibited cell growth in 12 of 16 DIPG cell lines in petri dishes, and when injected in mice, panobinostat inhibited DIPG cell growth and extended survival.
“Our results support the idea that histone modifications are the keys to understanding and treating DIPG,” said Michelle Monje, MD, PhD, assistant professor of neurology and neurological sciences at Stanford University School of Medicine and study author.
Eighty percent of DIPG tumors have a specific mutation, H3K27M, in a histone gene, indicating that panobinostat may be effective at treating a variety of DIPG tumors, including those with cells that do not have the mutation. For those cells that may develop a resistane to panobinostat over time, the researchers found that GSKJ4, another drug that blocks removal of methyl groups from histones, slowed DIPG tumor growth. Combining the two drugs appeared to slow DIPG cell growth even further, suggesting that they be used to treat tumors together.
Clinical trials to test the safety and effectiveness of panobinostat in children with DIPG are planned.
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