Current Perspectives on Pediatric Low-Grade Gliomas: Focus on BRAF and MEK Inhibition

Area of Science:

• Pediatric Oncology
• Molecular Biology
• Neuro-oncology

Background:

• Pediatric low-grade gliomas (pLGGs) represent the most frequent central nervous system tumors in children.
• These tumors are frequently characterized by alterations within the RAS/mitogen-activated protein kinase (RAS/MAPK) signaling pathway.
• Molecular profiling has identified key genetic drivers, including BRAF mutations and fusions.

Purpose of the Study:

• To review the molecular landscape of pLGG.
• To highlight current and emerging targeted therapies for pLGG.
• To discuss unresolved issues and future directions in pLGG treatment.

Main Methods:

• Literature review of molecular profiling data in pLGG.
• Analysis of clinical trial data for targeted therapies in pLGG.
• Synthesis of information on resistance mechanisms and toxicities.

Main Results:

• RAS/MAPK pathway alterations, particularly BRAF mutations/fusions, are common drivers in pLGG.
• First-generation BRAF and MEK inhibitors offer significant clinical benefits in specific patient subgroups.
• FDA approvals mark a shift from traditional chemotherapy towards targeted treatments.

Conclusions:

• Targeted therapies represent a paradigm shift in pLGG management.
• Addressing resistance, treatment durability, and long-term toxicities is crucial.
• Future directions involve optimizing treatment duration and toxicity management for individualized pLGG care.