Vismodegib
Vismodegib (trade name Erivedge  ERR-i-vej) is a drug for the treatment of basal-cell carcinoma (BCC). The approval of vismodegib on January 30, 2012, represents the first Hedgehog signaling pathway targeting agent to gain U.S. Food and Drug Administration (FDA) approval. The drug is also undergoing clinical trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma and chondrosarcoma as of June 2011. The drug was developed by the biotechnology/pharmaceutical company Genentech.

Indication
Vismodegib is indicated for patients with basal-cell carcinoma (BCC) which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation.

Mechanism of action
The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the Hedgehog signaling pathway. SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway. This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.

Side effects
In clinical trials, common side effects included gastrointestinal disorders (nausea, vomiting, diarrhoea, constipation), muscle spasms, fatigue, hair loss, and dysgeusia (distortion of the sense of taste). The effects were mostly mild to moderate.

Development
Vismodegib has undergone several promising phase I and phase II clinical trials for its use in treating medulloblastoma.

See also
Cyclopamine, a naturally occurring SMO antagonist

References
Further reading
Efficacy and Safety of Vismodegib

External links
"Vismodegib". Drug Information Portal. U.S. National Library of Medicine.
Food and Drug Administration (FDA) approved vismodegib