Journal
ONCOGENE
Volume 29, Issue 4, Pages 469-481Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2009.392
Keywords
hedgehog; smoothened; cancer; signal transduction; clinical trials and animal model
Funding
- National Cancer Institute [CA94160]
- Wells Center for Pediatric Research
- NATIONAL CANCER INSTITUTE [R01CA094160] Funding Source: NIH RePORTER
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The hedgehog pathway, initially discovered by two Nobel laureates Drs E Wieschaus and C Nusslein-Volhard in Drosophila, is a major regulator for cell differentiation, tissue polarity and cell proliferation. Studies from many laboratories reveal activation of this pathway in a variety of human cancer, including basal cell carcinomas (BCCs), medulloblastomas, leukemia, gastrointestinal, lung, ovarian, breast and prostate cancers. It is thus believed that targeted inhibition of hedgehog signaling may be effective in treatment and prevention of human cancer. 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. In this review, we will summarize major advances in the last 2 years in our understanding of hedgehog signaling activation in human cancer, interactions between hedgehog signaling and other pathways in carcinogenesis, potential antagonists for hedgehog signaling inhibition and their clinical implications for human cancer treatment. Oncogene (2010) 29, 469-481; doi:10.1038/onc.2009.392; published online 23 November 2009
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