Hedgehog signaling pathway: development of antagonists for cancer therapy.
The hedgehog pathway, initially discovered in Drosophila by two Nobel laureates, Dr. Eric Wieschaus and Dr. Christiane Nüsslein-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 nearly one third of extracutaneous human cancers, including medulloblastomas and gastrointestinal and prostate cancers. Even more exciting is the discovery and synthesis of specific signaling antagonists for the hedgehog pathway, which have significant clinical implications in novel cancer therapeutics. This review discusses the current understanding of the hedgehog signaling pathway and its activation in human cancers. It also discusses putative and confirmed signaling antagonists and their perspectives in therapeutic applications.
Xie
Jingwu
J
Sealy Center for Cancer Cell Biology, Department of Pharmacology and Toxicology, University of Texas at Galveston, 301 University Boulevard, Galveston, TX 77555, USA. jinxie@utmb.edu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor
D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor