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Vismodegib.

Frank Meiss1, Hana Andrlová2, Robert Zeiser2

  • 1Department of Dermatology and Venereology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstr. 7, 79104, Freiburg, Germany. frank.meiss@uniklinik-freiburg.de.

Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progres Dans Les Recherches Sur Le Cancer
|August 3, 2018
PubMed
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Vismodegib is a hedgehog (Hh) pathway inhibitor approved for advanced basal cell carcinoma (BCC). This targeted therapy blocks smoothened (SMO), controlling cancer cell growth in BCC and potentially other Hh-related cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The hedgehog (Hh) pathway is crucial for embryonic development but its aberrant activation drives cancer proliferation, notably in basal cell carcinoma (BCC).
  • Dysregulated Hh signaling is implicated in various cancers, including medulloblastoma, and cancers of the gastrointestinal tract, brain, lung, breast, and prostate.
  • Basal cell carcinoma (BCC) is a common skin cancer often linked to uncontrolled cell growth due to Hh pathway activation.

Purpose of the Study:

  • To review the mechanism of action and therapeutic applications of vismodegib, a novel Hh pathway inhibitor.
  • To highlight the regulatory approvals and clinical use of vismodegib for advanced basal cell carcinoma (BCC).
  • To discuss the potential for vismodegib in treating other malignancies beyond BCC.
Keywords:
Basal cell carcinomaHedgehog pathwayMedulloblastomaSmoothenedVismodegib

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Main Methods:

  • Literature review of preclinical and clinical studies on vismodegib.
  • Analysis of regulatory documents from the FDA and EMA regarding vismodegib approval.
  • Examination of the molecular interactions between vismodegib, smoothened (SMO), and the Hh pathway.

Main Results:

  • Vismodegib (GDC-0449, Erivedge®) effectively inhibits the Hh pathway by binding to smoothened (SMO).
  • Vismodegib received FDA approval in 2012 and EMA approval in 2013 for advanced BCC treatment.
  • The drug is indicated for patients with metastatic or surgically/radiotherapeutically inoperable locally advanced BCC.

Conclusions:

  • Vismodegib represents a significant advancement in targeted cancer therapy by inhibiting the Hh pathway.
  • Its efficacy in advanced BCC validates the Hh pathway as a therapeutic target.
  • Further investigation is warranted to explore vismodegib's role in treating other Hh-pathway-driven cancers.