Journal
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
Volume 40, Issue 7, Pages 670-680Publisher
OXFORD UNIV PRESS
DOI: 10.1111/j.1745-7270.2008.00431.x
Keywords
hedgehog; smoothened; PTCH1; human cancer therapy; basal cell carcinoma; antagonist
Categories
Funding
- NCI NIH HHS [R01 CA094160-06A2, R01 CA094160, CA94160] Funding Source: Medline
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The hedgehog (Hh) pathway, initially discovered in Drosophila by two Nobel laureates, Dr. Eric Wieschaus and Dr. Christiane Nusslein-Volhard, is a major regulator for cell differentiation, tissue polarity and cell proliferation. Studies from many laboratories, including ours, reveal activation of this pathway in most basal cell carcinomas and in approximately 30% of extracutaneous human cancers, including medulloblastomas, gastrointestinal, lung, breast and prostate cancers. Thus, it is believed that targeted inhibition of Hh signaling may be effective in treating and preventing many types of human cancers. Even more exciting is the discovery and synthesis of specific signaling antagonists for the Hh pathway, which have significant clinical implications in novel cancer therapeutics. This review discusses the major advances in the current understanding of Hh signaling activation in different types of human cancers, the molecular basis of Hh signaling activation, the major antagonists for Hh signaling inhibition and their potential clinical application in human cancer therapy.
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