Vismodegib Explained

Vismodegib, sold under the brand name Erivedge, is a medication used 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.^[1] 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.

Indication

Vismodegib is indicated for people 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.^[2]

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.^[3] 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).

Development

Vismodegib has undergone several promising phase I and phase II clinical trials for its use in treating medulloblastoma.^[4]

Further reading

• Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A . 6 . Efficacy and safety of vismodegib in advanced basal-cell carcinoma . The New England Journal of Medicine . 366 . 23 . 2171–2179 . June 2012 . 22670903 . 5278761 . 10.1056/NEJMoa1113713 .

External links

• Web site: Vismodegib . U.S. National Library of Medicine . Drug Information Portal .

Notes and References

1. Web site: FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma . Roche . 30 January 2012 . 9 August 2020.
2. Book: Lacroix M. Targeted Therapies in Cancer. 2014. Nova Sciences Publishers. Hauppauge, NY. 978-1-63321-687-7. 2014-07-13. 2015-06-26. https://web.archive.org/web/20150626172243/https://www.novapublishers.com/catalog/product_info.php?products_id=50994. dead.
3. Web site: Vismodegib (GDC-0449) Smoothened Inhibitor . https://web.archive.org/web/20110604073915/http://www.biooncology.com/pipeline-molecules/vismodegib/index.html . 4 June 2011 . BioOncology . Genentech .
4. Li Y, Song Q, Day BW . Phase I and phase II sonidegib and vismodegib clinical trials for the treatment of paediatric and adult MB patients: a systemic review and meta-analysis . Acta Neuropathologica Communications . 7 . 1 . 123 . July 2019 . 31362788 . 6668073 . 10.1186/s40478-019-0773-8 . free .