ABSTRACT

The hedgehog pathway is a major regulator for cell differentiation, tissue polarity and cell proliferation. Several studies reveal activation of this pathway in basal cell carcinomas in approximately 30% of extracutaneous solid tumors including medulloblastomas, lung, breast, gastrointestinal and prostate cancers. Targeted inhibition of hedgehog signaling may be effective in treatment of many types of human tumors. The discovery and synthesis of specific hedgehog antagonists raise the possibility of their successful use in human cancer therapy. In this review, the molecular basis of hedgehog signaling activation, major advances in our understanding of signaling activation in human solid tumors, hedgehog antagonists and their potential application in human cancer will be evaluated.