title: Sonidegib for the treatment of advanced basal cell carcinoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  All available papers from Medline and the abstracts of the most important dermato-oncology meetings were included.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Dermatology , University Hospital Zurich , Zurich , Switzerland.|b Centre of Dermatovenereology , Vilnius University , Vilnius , Lithuania.
authors.forename: Egle
authors.initials: E
authors.lastname: Ramelyte
authors.affiliation: a Department of Dermatology , University Hospital Zurich , Zurich , Switzerland.
authors.forename: Valerie C
authors.initials: VC
authors.lastname: Amann
authors.affiliation: a Department of Dermatology , University Hospital Zurich , Zurich , Switzerland.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000473:pathology; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D011725:Pyridines / Q000627:therapeutic use*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy*; D000072086:Smoothened Receptor / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D053823:Hedgehog Proteins; D011725:Pyridines; C491023:SMO protein, human; D000072086:Smoothened Receptor; C561435:sonidegib
keywords: Basal cell carcinoma; Hh inhibitor; SMO inhibitor; sonidegib