Can Panobinostat Be Effective for Diffuse Intrinsic Pontine Gliomas?

James Radke, PhD

In Nature Medicine, Grasso et al1 published their data showing the growth of tumor cell lines originating from children with diffuse intrinsic pontine gliomas (DIPG) could be slowed by the addition of histone deactetylase inhibitors, including panobinostat.

DIPG is an aggressive and lethal form of cancer that typically attacks children 4 to 9 years of age. Most children die within a year of the diagnosis and less than 1% longer than 5 years.

The study by Grasso and colleagues provides some hope for these children as they now can develop clinical trials to see if panobinostat is effective in the clinical setting. In a press release,2 senior author of the study, Michelle Monje, MD, PhD, assistant professor of neurology and neurological sciences at Stanford University School of Medicine, California, said “Our results provide a glimmer of hope for treating this heartbreaking disease.”

The multi-centered, collaborative study began 6 years ago, with a the help of funding from by the National Institutes of Health (NIH), the Department of Defense, and over 25 nonprofit foundations.

Jane Fountain, PhD, program director, at the National Institute of Neurological Disorders and Stroke (NINDS), part of the NIH said:

"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.”

The study tested 83 known or potential cancer drugs on each of the DIPG cell lines and found that histone deacetylase inhibitors consistently slowed DIPG growth.

The scientists also analyzed the genes of each cell line and after reviewing the genetic and screening data, they focused on Novartis’ panobinostat, a drug designed to block multiple types of histone deacetylases. In both in vitro studies and pre-clinical animal studies, panobinostat inhibited DIPG growth.

Dr. Monje said:

“Our results support the idea that histone modifications are the keys to understanding and treating DIPG.”

Clinical trials to test the safety and effectiveness of panobistat for children with DIPG is being planned by Dr. Monje, along with the National Cancer Institute-supported Pediatric Brain Tumor Consortium and Novartis.


1. Grasso CS, Tang Y, Berlow NE, et al. Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nature Medicine. [Published online May 4, 2015]. doi:10.1038/nm.3855.
2. Study points to possible treatment for lethal pediatric brain cancer [press release]. Bethesda, MD; National Institutes of Health; May 4, 2015.

Image courtesy of the NIH and the Monje lab, Stanford University, California.
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