INTRODUCTION: Advanced and metastatic basal cell carcinomas (BCCs) are rare but 
still present a severe medical problem. These tumors are often disfiguring and 
impact the quality of life by pain or bleeding. Based on discovery of the 
hedgehog (Hh) signaling pathway and its role in the pathogenesis of BCCs, 
smoothened (SMO) inhibitors have been developed with Sonidegib being the 2nd in 
class. It is the only Hh pathway inhibitor investigated in a randomized trial 
accompanied by pharmacodynamic investigations. Also, the disease assessment 
criteria applied were more stringent than those used in trials of 1st developed 
SMO inhibitor - vismodegib, and required annotated photographs, MRI as well as 
multiple biopsies in case of regression.
AREAS COVERED: All available papers from Medline and the abstracts of the most 
important dermato-oncology meetings were included.
EXPERT OPINION: Sonidegib is a promising medication for advanced BCC and other 
malignancies, driven by Hh signaling. It presents favorable pharmacokinetic 
properties and causes class specific toxicity with dose dependent adverse events 
in muscular and taste bud homeostasis, gastrointestinal symptoms and hair 
growth. Early after treatment initiation, it impacts the immunesusceptibility of 
the tumor lesions. Sonidegib deserves further development in combination with 
other drugs or antibodies, or alternative dosing schedules.