Vismodegib


Vismodegib is a drug for the treatment of basal-cell carcinoma. The approval of vismodegib on January 30, 2012, represents the first Hedgehog signaling pathway targeting agent to gain U.S. Food and Drug Administration approval. The drug is also undergoing clinical trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma and chondrosarcoma. The drug was developed by the biotechnology/pharmaceutical company Genentech, which is headquartered at South San Francisco, California, USA.

Indication

Vismodegib is indicated for patients with basal cell carcinoma 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 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 adverse effects included gastrointestinal disorders, muscle spasms, fatigue, hair loss, and dysgeusia. The effects were mostly mild to moderate.