New research offers hope for high-grade glioma treatment

High-grade glioma, an aggressive form of brain cancer affecting both paediatric and adult patients, remains one of the most challenging diseases to treat. The difficulty lies in the tumour’s location, its high rate of recurrence, and the blood-brain barrier – which prevents most drugs from effectively reaching the cancerous cells.

Researchers from the University of Michigan, Dana Farber Cancer Institute, and the Medical University of Vienna formed a collaborative team to address this need. Their study, published in Cancer Cell, uncovers a promising new avenue for treatment.

A new potential therapy

“We were excited to see that avapritinib essentially shut off PDGFRA signalling in mouse brain tumours,” said Dr Carl Koschmann, the ChadTough Defeat DIPG Research Professor and clinical scientific director of the Chad Carr Paediatric Brain Tumour Centre at C.S. Mott Children’s Hospital.

Given the limited effectiveness of existing treatments beyond surgery and radiation, Koschmann and his colleagues sought to explore new drug therapies. They focused on PDGFRA, one of the most commonly mutated genes in high-grade gliomas, as a potential target.

Overcoming the blood-brain barrier

One of the biggest challenges in treating brain cancer is ensuring that drugs can penetrate the blood-brain barrier. The research team screened multiple commercially available PDGFRA inhibitors and found avapritinib to be the strongest and most focused. Unlike many other drugs, avapritinib successfully crossed the blood-brain barrier in their study.

“When we gave mice the drug and showed that it reached the brain, we knew we were onto something,” said Kallen Schwark, a University of Michigan PhD student and one of the study’s lead authors.

While a clinical trial was not yet available, the research team was able to treat some patients with high-grade glioma through an expanded access program established by Blueprint. Across multiple international institutions, eight patients received avapritinib treatment, and the results were promising. The drug was well tolerated, and three of the eight patients showed tumour shrinkage.

This early data provided a strong foundation for further research. It helped justify the inclusion of paediatric high-grade glioma in a phase I paediatric solid tumour trial, which has recently completed patient enrolment and is now under analysis.

Future directions

“We have very few examples of drugs entering brain tumours like this and shutting down key oncogenic pathways,” he said. “These results support ongoing efforts to build on the success of avapritinib and other brain-penetrant small molecule inhibitors.”

Koschmann acknowledges that a single drug will not be sufficient to combat this devastating disease. The future of treatment will likely involve combinations of therapies that target multiple pathways, simultaneously. His team is already exploring the combination of avapritinib with MAP kinase inhibitors, which they believe could enhance treatment outcomes even further.

This study was published in Cancer Cell.