Redefining Pediatric Gliomas: Molecular Classification and the Evolution of Targeted Therapies

Brain tumors have now surpassed leukemia to become the most common malignancies in childhood. Gliomas, a subset of primary central nervous system (CNS) tumors characterized by glial morphology, are the most prevalent of these tumors and can be either high- or low-grade. Prognosis and therapeutic approaches significantly differ between high-grade and low-grade gliomas, with generally poor survival rates for pediatric high-grade gliomas (pHGG) and more favorable outcomes for low-grade gliomas (pLGG). Historically, treatment has consisted of maximally safe surgical resection with or without radiation or chemotherapy, with the therapeutic plan dictated by age, tumor histology, grading and the extent of resection. However, extensive investigation into the molecular drivers of tumorigenesis over the last two decades has improved our understanding of glioma biology, resulting in changes to the classification criteria for these tumors as well as the development of new therapeutic agents targeting critical oncogenic pathways. This has begun to shift clinical practice for some tumor types, such as BRAF-altered LGG. In this review, we summarize our current classification of pediatric gliomas as well as their pathogenesis and treatment, with a particular focus on how biological insights have led to changes in current clinical practice, as well as how ongoing studies in tumor biology may evolve into the next generation of novel treatment strategies.