Pediatric high-grade gliomas (HGGs)--including glioblastoma multiforme, 
anaplastic astrocytoma, and diffuse intrinsic pontine glioma--are difficult to 
treat and are associated with an extremely poor prognosis. There are no 
effective chemotherapeutic regimens for the treatment of pediatric HGG, but many 
new treatment options are in active investigation. There are crucial molecular 
differences between adult and pediatric HGG such that results from adult 
clinical trials cannot simply be extrapolated to children. Molecular markers 
overexpressed in pediatric HGG include PDGFRα and P53. Amplification of EGFR is 
observed, but to a lesser degree than in adult HGG. Potential molecular targets 
and new therapies in development for pediatric HGG are described in this review. 
Research into bevacizumab in pediatric HGG indicates that its activity is less 
than that observed in adult HGG. Similarly, tipifarnib was found to have minimal 
activity in pediatric HGG, whereas gefitinib has shown greater effects. After 
promising phase I findings in children with primary CNS tumors, the integrin 
inhibitor cilengitide is being investigated in a phase II trial in pediatric 
HGG. Studies are also ongoing in pediatric HGG with 2 EGFR inhibitors: cetuximab 
and nimotuzumab. Other novel treatment modalities under investigation include 
dendritic cell-based vaccinations, boron neutron capture therapy, and telomerase 
inhibition. While the results of these trials are keenly awaited, the current 
belief is that multimodal therapy holds the greatest promise. Research efforts 
should be directed toward building multitherapeutic regimens that are well 
tolerated and that offer the greatest antitumor activity in the setting of 
pediatric HGG.