Title:Therapeutic Targeting of Developmental Signaling Pathways in Medulloblastoma: Hedgehog, Notch, Wnt and Myc
VOLUME: 8 ISSUE: 1
Author(s):Eric Raabe and Charles G. Eberhart
Affiliation:Departments of Pediatrics, Oncology, Pathology and Ophthalmology, Johns Hopkins University.
Keywords:Non-genotoxic therapy, primitive neuroectodermal tumor, gamma secretase, tankyrase, glutamine, cyclopamine,
itraconazole
Abstract:During development of the cerebellum, a large number of molecular factors interact to produce an intricate
brain structure. Many of these developmentally significant genes are members of signaling cascades implicated in the
formation and growth of the embryonal brain tumor medulloblastoma. Genes controlling critical developmental pathways
such as Hedgehog, Notch, Wnt, and Myc are known to be overexpressed and/or genetically altered in subsets of
medulloblastoma. These pathways are also linked by their ability to induce or maintain stem-cell phenotypes in normal
development. Their over-activation in tumors can lead to proliferation, invasion, altered metabolism, and evasion of
treatment-induced cell death. The importance of these signaling cascades in medulloblastoma cells makes them attractive
targets for therapeutic intervention. The development of therapeutic agents targeting these pathways may lead to
improvement in patient survival and a reduction in the intensity of highly morbid radiation and chemotherapy that patients
currently receive. In this review, we discuss a number of approaches to targeting these pathways in medulloblastoma.
