Tumors of the Central Nervous System (CNS) are the most common solid
tumors in children, and represent a heterogeneous group of diseases. Progress has been
made in understanding the biology of some histologic tumor subtypes and a number of
involved cell signaling pathways have been identified. As a consequence, molecularly
targeted therapies are being evaluated as part of the therapeutic armamentarium against
these diseases. Targeting key signaling pathways in pediatric brain tumors is an attractive
idea since aberrant signaling pathways may be specific to tumor cells. Pediatric tumors are
different from their adult counterparts and offer unique challenges. In addition to the
unique pharmacokinetic properties of the CNS (blood-brain barrier and blood-tumor
barrier), treatment of children with brain tumors is aimed at the developing brain, which
may be more susceptible to effects of therapy, and the effects of signal inhibitors on the
post-natal developing brain are largely unknown. Despite these obstacles, inhibitors of
signaling networks involving sonic hedgehog, epidermal growth factor receptor, plateletderived
growth factor receptor, BRAF, Notch, and others are under clinical investigation
and have the potential to bring exciting management alternatives for pediatric CNS tumors
in the near future. This article reviews pediatric brain tumors with signaling pathways
implicated in their tumorigenesis and current efforts to target them.
Keywords: Astrocytoma, early phase clinical trials, ependymoma, glioblastoma,
glioma, kinase inhibitor, medulloblastoma, molecularly targeted therapy, pediatric
brain tumor, signaling pathway.
