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Vismodegib

Vismodegib, sold under the brand name Erivedge, is a medication used for the treatment of basal-cell carcinoma (BCC).[3] 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.[4] 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.[5] The drug was developed by the biotechnology/pharmaceutical company Genentech.[4]

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.[4][6]

Mechanism of action

The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the Hedgehog signaling pathway.[5] SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway.[7] This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas.[8]

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).[3]

Development

Vismodegib has undergone several promising phase I and phase II clinical trials for its use in treating medulloblastoma.[9]

References

  1. ^ a b "Erivedge® (vismodegib)". Australian Prescribing Information, Australian Register of Therapeutic Goods (ARTG). Roche Products Pty Limited. 17 November 2022.
  2. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  3. ^ a b c "Erivedge- vismodegib capsule". DailyMed. U.S. National Library of Medicine. 9 April 2019. Retrieved 8 January 2023.
  4. ^ a b c "FDA approves Erivedge (vismodegib) capsule, the first medicine for adults with advanced basal cell carcinoma". Roche. 30 January 2012. Retrieved 9 August 2020.
  5. ^ a b "Vismodegib". Molecule of the Month. Prous Science. June 2011. Archived from the original on 27 September 2011.
  6. ^ Lacroix M (2014). Targeted Therapies in Cancer. Hauppauge, NY: Nova Sciences Publishers. ISBN 978-1-63321-687-7. Archived from the original on 2015-06-26. Retrieved 2014-07-13.
  7. ^ "Vismodegib (GDC-0449) Smoothened Inhibitor". BioOncology. Genentech. Archived from the original on 4 June 2011.
  8. ^ Spreitzer H (4 July 2011). "Neue Wirkstoffe – Vismodegib". Österreichische Apothekerzeitung (in German) (14/2011): 10.
  9. ^ Li Y, Song Q, Day BW (July 2019). "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. doi:10.1186/s40478-019-0773-8. PMC 6668073. PMID 31362788.

Further reading

External links