Smoothened inhibitors in the treatment of advanced basal cell carcinomas.
OBJECTIVE
The Hedgehog pathway has been identified as a key element in the development of many forms of cancer. Smoothened (Smo) inhibitors are known to beneficially interfere with the Hedgehog pathway and are currently under investigation as anticancer drugs for many tumor entities. Reviewed here are the most recent developments in clinical research on Smo inhibitors for the treatment of advanced basal cell carcinoma (BCC).


RESULTS
When reviewing the literature of the past 12 months, it is striking to see the rapid evolution of the field. Compounds that have been presented as powerful new drug candidates 12 months ago have now been discontinued, whereas new ones have emerged. Reports on 13 drug candidates have been identified: one marketed, vismodegib, eight currently under development (phase I-II) and four for which clinical investigation for BCC is currently not being pursued.


CONCLUSIONS
Smo inhibitors are a promising drug class for the treatment of BCC. To date, most candidates are in early stage development and are expected to enter the market in approximately 5-8 years, if successful.
Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Rainer
R
Kunstfeld
D000813:Anilides / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D011725:Pyridines / Q000627:therapeutic use*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000072086:Smoothened Receptor; D016019:Survival Analysis; D016896:Treatment Outcome
D000813:Anilides; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor