Hedgehog Signaling in Pediatric Brain Tumors

  • Joon Won Yoon
  • Jason Fangusaro
  • Philip Iannaccone
  • David Walterhouse


Dysregulation of the Sonic hedgehog (SHH) signal transduction ­pathway is observed in a variety of developmental disorders of the central nervous system and in some brain tumors. During development, SHH signaling contributes to establishing a dorso-ventral axis within the neural tube, proliferation of cells in the region of the developing brain and ultimately brain growth, establishing inter-brain boundaries, and establishing regional specificity within the brain. SHH signaling contributes to the development of the cerebellum through paracrine signaling from Purkinje cells to cerebellar granule precursors (CGP) and promotes CGP proliferation. It is believed that mutations in components of the pathway cause constitutive pathway activation in CGPs, which contributes to the development of some medulloblastomas. Medulloblastoma is the most common malignant pediatric brain tumor. Current therapy includes a combination of surgery, chemotherapy, and radiotherapy. Inhibition of the Hedgehog signaling pathway or genes and pathways that modulate Hedgehog signaling represent a novel strategy to possibly improve outcomes with less toxicity for some patients with medulloblastoma and potentially other pediatric brain tumors. Hedgehog pathway inhibitors are being developed and early phase clinical trials are underway. Optimal efficacy with these agents may require combinations with agents targeting other pathways and genes that play roles in CGP development and in modulating Hedgehog signaling in medulloblastoma.


Sonic hedgehog Central nervous system Cerebellum Pediatric brain tumors Medulloblastoma Hedgehog inhibitors 


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Joon Won Yoon
    • 1
  • Jason Fangusaro
  • Philip Iannaccone
  • David Walterhouse
  1. 1.Department of Pediatrics, Developmental Biology Program, Children’s Memorial Research CenterNorthwestern University, Feinberg School of Medicine and Children’s Memorial HospitalChicagoUSA

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