Implications of hedgehog signaling antagonists for cancer therapy

Authors

  • Jingwu Xie

    Corresponding author
    1. Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology, University of Texas at Galveston, Galveston, Texas 77555-1048, USA
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  • This work was supported by the grants from the National Cancer Institute (CA94160, DOD PC030429) and the AGA Foundation

*Corresponding author: Tel, 1-409-747-1845; Fax, 1-409-747-1938; E-mail, jinxie@utmb.edu

Abstract

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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