The hedgehog pathway and basal cell carcinomas

Developmental pathways first elucidated by genetic studies in the fruit fly , Drosophila melanogaster, are conserved in vertebrates, and disruption of these pathways has been associated with various human congenital anomalies. Many developmental genes continue to play an important role in regulation of cell growth and differentiation after embryogenesis, and mutations in so me of these genes can result in cancer. Basal cell carcinoma (BCC) of the s kin is the most common type of cancer in humans. Although most BCCs are spo radic, in rare cases, individuals have a hereditary disease, Gorlin syndrom e, that predisposes to multiple skin tumors as well as a variety of birth d efects, Mutations in the human homolog of a Drosophila gene, patched underl ie Gorlin syndrome. Genetic studies in Drosophila show that patched is part of the hedgehog signaling pathway, important in determining embryonic patt erning and cell fate in multiple structures of the developing embryo. Human patched is mutated in sporadic as well as hereditary BCCs, and inactivatio n of this gene is probably a necessary if not sufficient step for tumor for mation. Delineation of the biochemical pathway in which patched functions m ay lead to rational medical therapy for skin cancer and possibly other tumo rs.