Targeting the Hedgehog Pathway in Pediatric Medulloblastoma

Cancers

Sherri Y. Huang²  Jer-Yen Yang¹ 

[1] Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47906, USADepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA;

关键词: hedgehog;    Gli1;    medulloblastoma;   

DOI  :  10.3390/cancers7040880

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.