Sonidegib for the treatment of advanced basal cell carcinoma.
- Ramelyte E a Department of Dermatology , University Hospital Zurich , Zurich , Switzerland.
- Amann VC a Department of Dermatology , University Hospital Zurich , Zurich , Switzerland.
- Dummer R a Department of Dermatology , University Hospital Zurich , Zurich , Switzerland.
- 2016-08-19
Published in:
- Expert opinion on pharmacotherapy. - 2016
Basal cell carcinoma
Hh inhibitor
SMO inhibitor
sonidegib
Antineoplastic Agents
Biphenyl Compounds
Carcinoma, Basal Cell
Hedgehog Proteins
Humans
Pyridines
Quality of Life
Randomized Controlled Trials as Topic
Signal Transduction
Skin Neoplasms
Smoothened Receptor
English
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.
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.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1080/14656566.2016.1225725
- PMID 27538055
- Persistent URL
- https://sonar.ch/global/documents/36017
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