Sonic hedgehog signaling in basal cell carcinomas

The development of basal cell carcinoma, the commonest human cancer in fair skinned populations, is clearly associated with constitutive activation of sonic hedgehog signaling. Insight into the genesis of BCC came from the identification of germline mutations of the tumor suppressor gene, PATCHED, a key regulatory component of hedgehog signaling in the nevoid basal cell carcinoma syndrome. Analysis of sporadic basal cell carcinomas and those from repair deficient xeroderma pigmentosum patients has revealed mutational inactivation of PATCHED and gain of function mutations of the proto-oncogenes, SMOOTHENED and SONIC HEDGEHOG associated with solar UV exposure. The molecular mechanisms involved in alterations of the hedgehog signaling pathway that lead to the formation of basal cell carcinomas are being unraveled and has already allowed the investigation of future therapeutic strategies for treating these skin cancers.