Activation of Hedgehog pathway in gastrointestinal cancers

The hedgehog (Hh) pathway is a major regulator for cell differentiation, tissue polarity, and cell proliferation in embryonic development and homeostasis in adult tissue. 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 Hh 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 Hh pathway, which have significant clinical implications in novel cancer therapeutics. In this review, we summarize major advances in the past 2 years in our understanding of Hh signaling activation in human gastrointestinal cancer and their potential in clinical treatment with Hh pathway inhibitors.