2001 Volume 111 Issue 6 Pages 925-930
Since the discovery that inactivation of the human patched gene is responsible for the nevoid basal cell carcinoma syndrome and sporadic forms of basal cell carcinoma (BCC), a role for dysregulation of hedgehog signaling in tumorigenesis of BCC has been firmly established. Other key members of this pathway, such as sonic hedgehog, smoothened, and the Gli family of transcriptional factors, have also been shown to be involved in tumor formation of BCC. Recently, the plant-derived teratogen cyclopamine has been shown to inhibit the hedgehog response and is expected as a potential `mechanism-based’ therapeutic agent for the treatment of BCC. Dysregulation of hedgehog signaling was also demonstrated in trichoepithelioma, which has morphological similarity to BCC. However, whether other appendageal tumors including trichoblastomas and those arising from nevus sebaceous also include hedgehog signaling abnormalities is controversial. For extramammary Paget’s disease, new therapeutic approaches targeting the erbB-2 oncogene and possible androgen dependence of this tumor have been suggested. An innovative technology of DNA microarrays, which allows the mathematical analysis of expression of thousands of genes, has recently been introduced in genetic analysis for melanoma. This analysis may identify unrecognized subtypes of cutaneous melanoma with different biological potentials.
