Clinical implications of hedgehog signaling pathway inhibitors.
- Author:
Hailan LIU
1
;
Dongsheng GU
;
Jingwu XIE
Author Information
1. Wells Center for Pediatric Research, Division of Hematology and Oncology, Department of Pediatrics, Indiana University Simon Cancer Center, Indiana University, Indianapolis, Indiana 46202, USA.
- Publication Type:Journal Article
- MeSH:
Animals;
Antineoplastic Agents;
therapeutic use;
Basal Cell Nevus Syndrome;
drug therapy;
metabolism;
Carcinoma, Basal Cell;
drug therapy;
metabolism;
Cell Differentiation;
Cerebellar Neoplasms;
drug therapy;
metabolism;
Hedgehog Proteins;
antagonists & inhibitors;
metabolism;
Humans;
Medulloblastoma;
drug therapy;
metabolism;
Models, Animal;
Neoplasms;
drug therapy;
metabolism;
Patched Receptors;
Receptors, Cell Surface;
genetics;
metabolism;
Signal Transduction;
drug effects;
Skin Neoplasms;
drug therapy;
metabolism
- From:Chinese Journal of Cancer
2011;30(1):13-26
- CountryChina
- Language:English
-
Abstract:
Hedgehog was first described in Drosophila melanogaster by the Nobel laureates Eric Wieschaus and Christiane Nüsslein-Volhard. The hedgehog (Hh) pathway is a major regulator of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer was established through studies of a rare familial disease, Gorlin syndrome, in 1996. Follow-up studies revealed activation of this pathway in basal cell carcinoma, medulloblastoma and, leukemia as well as in gastrointestinal, lung, ovarian, breast, and prostate cancer. Targeted inhibition of Hh signaling is now believed to be effective in the treatment and prevention of human cancer. The discovery and synthesis of specific inhibitors for this pathway are even more exciting. In this review, we summarize major advances in the understanding of Hh signaling pathway activation in human cancer, mouse models for studying Hh-mediated carcinogenesis, the roles of Hh signaling in tumor development and metastasis, antagonists for Hh signaling and their clinical implications.
