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Cancers 2015, 7(4), 2110-2123; doi:10.3390/cancers7040880

Targeting the Hedgehog Pathway in Pediatric Medulloblastoma

1
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
2
Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47906, USA
3
Center for Cancer Research, Purdue University, West Lafayette, IN 47906, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Hui-Wen Lo
Received: 12 August 2015 / Revised: 5 October 2015 / Accepted: 16 October 2015 / Published: 23 October 2015
View Full-Text   |   Download PDF [557 KB, uploaded 23 October 2015]   |  

Abstract

Medulloblastoma (MB), a primitive neuroectomal tumor of the cerebellum, is the most common malignant pediatric brain tumor. The cause of MB is largely unknown, but aberrant activation of Hedgehog (Hh) pathway is responsible for ~30% of MB. Despite aggressive treatment with surgical resection, radiation and chemotherapy, 70%–80% of pediatric medulloblastoma cases can be controlled, but most treated patients suffer devastating side effects. Therefore, developing a new effective treatment strategy is urgently needed. Hh signaling controls transcription of target genes by regulating activities of the three Glioma-associated oncogene (Gli1-3) transcription factors. In this review, we will focus on current clinical treatment options of MB and discuss mechanisms of drug resistance. In addition, we will describe current known molecular pathways which crosstalk with the Hedgehog pathway both in the context of medulloblastoma and non-medulloblastoma cancer development. Finally, we will introduce post-translational modifications that modulate Gli1 activity and summarize the positive and negative regulations of the Hh/Gli1 pathway. Towards developing novel combination therapies for medulloblastoma treatment, current information on interacting pathways and direct regulation of Hh signaling should prove critical View Full-Text
Keywords: hedgehog; Gli1; medulloblastoma hedgehog; Gli1; medulloblastoma
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Huang, S.Y.; Yang, J.-Y. Targeting the Hedgehog Pathway in Pediatric Medulloblastoma. Cancers 2015, 7, 2110-2123.

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