Promising Advances in Targeted Treatments for Pediatric Gliomas

Recent findings from a collaborative study involving Dana-Farber Cancer Institute and the Broad Institute indicate significant potential for targeted therapies in treating pediatric gliomas, the most prevalent type of brain tumor among children. The research revealed that approximately 8.9% of pediatric glioma cases exhibit alterations in the fibroblast growth factor receptor (FGFR) family of proteins, suggesting that these tumors may respond favorably to existing FDA-approved FGFR inhibitors.

The implications of this research are particularly relevant for low-grade gliomas (pLGG) in children. Despite the promising results, further investigations are essential to enhance the efficacy of these treatments and to initiate pediatric clinical trials, as there are currently no FDA-approved therapies or clinical trials specifically addressing FGFR-altered pediatric gliomas.

The study was driven by the urgent need to provide options for patients diagnosed with pediatric gliomas featuring FGFR alterations. Insights gained from this research could significantly impact the care of children with these conditions seeking treatment at facilities like the Jimmy Fund Clinic.

The findings are published in Nature Communications. Similar prior research at Dana-Farber led to the approval of tovorafenib for treating childhood BRAF-altered gliomas, and the team hopes to apply this strategy to FGFR-altered pediatric gliomas, which remain an area of critical need for affected families.

The study, led by pathologist Keith Ligon, MD, PhD, involved genomic analyses of 11,635 gliomas sourced from three existing datasets across various ages. This comprehensive analysis highlighted that 8.9% of pediatric gliomas present FGFR alterations, primarily involving the FGFR1 and FGFR2 genes, with both point mutations and structural variants identified. The research concluded that FGFR1-altered pLGGs constitute the most common subgroup of FGFR-altered gliomas in children.

Co-first authors, April Apfelbaum, PhD, and Eric Morin, MD, PhD, developed the first models of FGFR-altered gliomas using living FGFR-altered neural stem cells. Their research demonstrated that FGFR alterations could stimulate tumor development, and subsequent tests indicated that these tumors exhibited sensitivity to FGFR inhibitors.

This study marks the first preclinical evidence supporting the viability of existing FGFR inhibitors as potential treatments for FGFR-altered pediatric gliomas. Further retrospective analysis of a small cohort of pediatric patients treated with FGFR inhibitors revealed that many experienced stable disease following treatment.

Pediatric low-grade gliomas represent the most common central nervous system cancers in children. While many patients can expect to survive into adulthood, standard treatments involving chemotherapy and surgery often result in long-term complications, including mental health issues, vision impairment, seizures, and behavioral challenges.

Researchers are dedicated to discovering precision medicines that present fewer side effects compared to current standard care options. Future research will aim to improve the effectiveness and brain penetration of FGFR inhibitors, along with testing these treatments in clinical trials. The team also plans to explore the role of FGFR expression in normal brain development, which may influence treatment strategies.

Overall, this groundbreaking research opens new avenues for targeted therapies that could significantly improve the treatment landscape for pediatric gliomas.