Frontiers in Clinical Drug Research - Anti-Cancer Agents

Volume: 1

Targeting Key Signaling Pathways in Pediatric Brain Tumors

Author(s): Fernanda I. Arnaldez and Katherine E. Warren

Pp: 239-267 (29)

DOI: 10.2174/9781608057986113010007


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.

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