The sonic hedgehog pathway is implicated in the development of skin cancers called basal cell carcinoma (BCC). The mutation in nevoid basal cell carcinoma syndrome (NBCCS) (also called Gorlin’s syndrome) is at the level of the patched protein (PTCH) which is located on chromosome 9. PTCH is an inhibitor of smoothened (Smo), which is the protein which is at the top of the sonic hedgehog activation pathway. This mutation has also been demonstrated in sporadic basal cell carcinomas.

LDE225 is an inhibitor of Smo. Therefore it was evaluated as a topical inhibitor of BCC in patients with NBCCS. 8 patients with NBCCS and 27 BCC’s were treated with 0.75% LDE225 cream (or a control consisting of the excipient (vehicle) only) (randomised double-blind study) for 4 weeks. 3 complete clinical responses, 9 partial responses and one with no response were observed. With the excipient only, no responses were observed in 14 patients except in one who showed a partial response. The cases labeled as succesfully showing a complete clinical response also failed to show histological clearance. It is worth mentioning that the treatment is well tolerated: nothing apart from irritation is mentioned.

Other molecules have also been shown to inhibit pathway activation, such as cyclopamine. However the study presented here shows a clinically successful application of Smo inhibition in patients with NBCCS. It remains to be demonstrated on a larger scale (more patients and longer treatment duration) and it would be interesting to see if the treatment is also effective in sporadic (sporadic) basal cell carcinoma.



Source of information. Stingl G. Treatment of nevoid basal cell carcinoma using a topically applied smoothened antagonist. 19th Annual Congress of the European Academy of Dermatology and Venereology (EADV) – Gothenburg (Göteborg), Sweden (Sverige) 2010. Satellite symposium organized and funded by Novartis.