Basal cell carcinomas: attack of the hedgehog

Abstract

Basal cell carcinomas (BCCs) are keratinocyte tumours that resemble the basal layer of the epidermis, and are the most commonly diagnosed human cancer among persons of European ancestry. Despite this high frequency, the death rate is extraordinarily low, a reflection perhaps of the excellent care provided by physicians and of their vanishingly rare propensity to metastasize. The vast majority of BCCs occur sporadically, but patients with the rare heritable disorder basal cell nevus syndrome (BCNS) have a marked susceptibility to developing BCCs. Family based linkage studies of kindreds with BCNS identified the patched 1 (PTCH1) gene, an inhibitor of the hedgehog signalling pathway, as being mutated in these patients. p53 is also mutated in some patients with sporadic BCCs. Downstream signalling pathways that are deregulated in patients with BCCs are currently being investigated. Surgery is curative for most patients with BCCs. However, for those few that develop locally advanced or metastatic BCC, for which there is currently no effective treatment, Phase I clinical trials with inhibitors of the hedgehog signalling pathway have produced promising results.