The FGF/FGFR System in the Biology and Therapeutic Landscape of Pediatric CNS Tumors.

Abstract

Central nervous system (CNS) tumors are the most common solid malignancies in children, comprising a highly heterogeneous group of neoplasms defined by distinct molecular alterations and clinical behaviors. Advances in molecular genetics have underscored the relevance of specific signaling pathways in driving pediatric tumorigenesis, among which the fibroblast growth factors (FGFs) and their receptors (FGFRs) have emerged as critical regulators of CNS development and tumor biology. The strict regulation of this system is frequently disrupted in cancer contexts, leading to abnormal activation that promotes tumor growth, invasion, and therapy resistance. Recent genomic profiling studies confirm that FGFR gene aberrations (i.e., activating point mutations, amplifications, and fusions) occur in a non-negligible fraction of pediatric CNS tumors. Notably, FGFR alterations are found in approximately 9% of pediatric gliomas, representing a higher incidence compared to adult gliomas. Across a broader survey of pediatric solid and brain tumors, activating FGFR aberrations were measurable in approximately 3% of cases. This prevalence establishes the FGF/FGFR axis as a measurable therapeutic vulnerability in defined patient subsets. Therefore, a deeper understanding of the role of the FGF/FGFR system across different pediatric CNS tumor subtypes is essential for elucidating disease mechanisms and identifying novel therapeutic opportunities. This review outlines the characteristics of major pediatric CNS tumors and discusses the role and potential therapeutic targeting of the FGF/FGFR system.