The Sonic Hedgehog Signaling Network in Development and Neoplasia

The sonic hedgehog (SHH) pathway was first defined genetically in fruit flies. Subsequently, the SHH network has been shown to be critical for normal mammalian development, by mediating interactions between stromal and epithelial cells. Recent evidence suggests that, deregulation of SHH signaling is important in the pathogenesis of cancer. Further, some observations suggest that a SHH paracrine mechanism mediating tumor-mesenchymal interactions may contribute to the metastatic capacity of cancer. Preclinical studies demonstrate that tumor cells in which SHH is deregulated are dependent on signaling through this pathway for the maintenance of proliferation and viability. SHH antagonists have been identified and show promise in inhibiting tumor growth in preclinical studies. The utility of these agents in the management of cancer patients awaits the outcome of ongoing and future clinical trials.