New Potential Treatment Approach for Pediatric High-Grade Gliomas

Pediatric high-grade gliomas (pHGG) are known for their poor prognosis, but researchers have recently identified a promising new treatment strategy. Each year, approximately 2,200 children and adolescents in Germany are diagnosed with cancer, with central nervous system tumors such as gliomas being the most common solid tumors in this age group. pHGGs, in particular, are characterized by their aggressive nature and difficulty in treatment.

A research team from the Department of Pediatric Oncology at Harvard Medical School in Boston has made significant strides in understanding pHGG. Their findings, based on tissue samples, reveal that this type of cancer often features genetic mutations or an elevated presence of the Platelet-Derived Growth Factor Receptor Alpha (PDGFRA). This receptor interacts with the PDGF growth factor, which promotes cancer proliferation through multiple mechanisms.

The team's study, published in the journal Cancer Cell, indicates that PDGFRA can be selectively inhibited using the tyrosine kinase inhibitor Avapritinib. This drug is already approved for adult use, specifically in treating advanced gastrointestinal stromal tumors that exhibit specific PDGFRA mutations.

Early positive results have emerged from the study, where approximately 15% of the 261 tissue samples examined exhibited PDGFRA mutations and/or an increased number of gene copies. Previous attempts to block PDGFRA in pHGG have seen limited success, primarily due to poor tolerability and insufficient penetration of the treatment into the central nervous system, according to statements from the Medical University of Vienna, where the study leader is based.

In laboratory and animal models, the research demonstrated that Avapritinib effectively inhibits PDGFRA and successfully crosses the blood-brain barrier in both mice and humans. The alterations in PDGFRA found in high-grade gliomas contribute to their increased aggressiveness and growth, but they also present a potential target for effective therapeutic strategies.

Initial clinical experiences with Avapritinib in children and young adults suffering from predominantly recurrent or refractory PDGFRA-altered high-grade gliomas have shown that the treatment is well tolerated. In three out of seven cases, radiotherapy yielded a positive response. Tumors with specific PDGFRA mutations that had previously resisted standard treatment through radiation have responded to this innovative therapeutic approach. These findings provide a foundation for an international clinical Phase 1/2 study and additional combination studies involving Avapritinib for pediatric high-grade gliomas with PDGFRA alterations.