Christopher Hubert, PhD

Lerner Research Institute

PEDIATRIC BRAIN CANCER

Pediatric Pilot Award

Investigation and Therapeutic Exploitation of BMX as a Biomarker of Hypersensitivity to Ibrutinib in Pediatric High-Grade Glioma

High grade glioma (HGG) is a deadly brain cancer in both adults and children. Patients with this cancer rarely survive beyond 3-5 years from diagnosis. Radiation therapy directed at the tumor is the standard treatment approach to slow tumor growth. Our research plans to combine radiation therapy with a medication called ibrutinib to increase cancer cell death in children with HGG. The combination of radiation with ibrutinib is currently being investigated at our institute in adult patients with this cancer. Through this adult clinical trial, we have found that some HGGs respond better than others to the combination of radiotherapy and ibrutinib, but we have not known why. We are investigating biological molecules, called biomarkers, that can help predict the likelihood that ibrutinib will work for each specific patient with HGG. The protein BMX is highly expressed in HGG, promotes cancer cell growth, and is likely responsible for resisting treatment with ibrutinib. BMX levels are comparatively low in pediatric HGG, and pediatric specimens are highly sensitive to ibrutinib in laboratory experiments. Our research will first investigate whether high levels of BMX correlate with ibrutinib resistance in adult HGG specimens from the current clinical trial. This data will help current adult and future pediatric patient selection, increasing the likelihood that ibrutinib will effectively increase cancer cell death in selected patients. We will then explore ibrutinib response in preclinical pediatric HGG models with the intention to run a clinical trial in children with HGG using ibrutinib and radiation therapy in combination.

IN OTHER WORDS

Our research plans to combine radiation therapy with a medication called ibrutinib to increase cancer cell death in children with brain cancer. We want to figure out if a protein found in a lab marks whether or not patients will respond to a particular therapy. Based off of these findings, we want to find out if we should start therapeutic trials in children with brain tumors.