Targeting the Hedgehog pathway in cancer

The hedgehog (Hh) signalling pathway is a key regulator of embryonic development, and its deregulation is associated with various birth defects.Although mostly quiescent in adult tissues, Hh signalling has recently been recognized to participate in tissue repair and tumour growth.Basal cell carcinoma and medulloblastoma, two cancers that involve mutation-driven upregulation of Hh signalling, were the first cancers shown to involve the Hh pathway.Numerous other solid tumours, including pancreatic and prostate cancers, are now thought to have hyper-activated Hh signalling. In these cases, the signalling is stimulated by excessive production of Hh ligands by tumour cells.Several families of small-molecule Hh inhibitors have been identified and are in varying stages of clinical development.The pleiotropic nature of the Hh pathway, seen to be involved in tumour-cell and tumour stem-cell proliferation, as well as in angiogenesis, suggests that Hh antagonists might constitute, under some circumstances, an exciting new type of cancer treatment.