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Pediatric Medulloblastoma: Pituitary Adenylyl Cyclase Activating Peptide/Protein Kinase A Antagonism of Hedgehog Signaling

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Pediatric Cancer, Volume 3

Part of the book series: Pediatric Cancer ((PECA,volume 3))

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Abstract

Medulloblastoma is a highly malignant pediatric brain tumor thought to commonly arise from cerebellar precursor cells that exhibit increased hedgehog signaling. Several treatment modalities, including surgical resection, radio- and chemo-therapy have enhanced the survival rates of individuals with medulloblastoma. However, significant adverse effects from some of these approaches in the developing brain necessitate the development of targeted molecular therapeutics that will minimize toxicity while maximizing tumor regression and eradication. Recent evidence suggests that the neuropeptide pituitary adenylyl cyclase activating polypeptide (PACAP) – a neuropeptide highly expressed and implicated in the development of the cerebellum and other neural structures – may play an important role in the development of medulloblastoma. Via activation of cAMP-dependent protein kinase A (PKA), PACAP negatively regulates the hedgehog pathway both in cerebellar development and medulloblastoma pathogenesis. The PACAP/PKA signaling pathway may therefore offer a novel therapeutic target to minimize the tumor burden in the pediatric population suffering from medulloblastoma.

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Authors and Affiliations

  1. Semel Institute, Department of Psychiatry and Biobehavioural Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA

    Joseph R. Cohen Ph.D. & James A. Waschek Ph.D.

  2. Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA

    Linda M. Liau Ph.D.

Authors
  1. Joseph R. Cohen Ph.D.
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  2. Linda M. Liau Ph.D.
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  3. James A. Waschek Ph.D.
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Corresponding author

Correspondence to Joseph R. Cohen Ph.D. .

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Editors and Affiliations

  1. Biology, Kean University, Union, New Jersey, USA

    M.A. Hayat

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Cohen, J.R., Liau, L.M., Waschek, J.A. (2012). Pediatric Medulloblastoma: Pituitary Adenylyl Cyclase Activating Peptide/Protein Kinase A Antagonism of Hedgehog Signaling. In: Hayat, M. (eds) Pediatric Cancer, Volume 3. Pediatric Cancer, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4528-5_14

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