Sonidegib

Mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

Sachin Jain, Ruolan Song, Jingwu Xie

Research output: Contribution to journalReview article

19 Citations (Scopus)

Abstract

The Hedgehog (Hh) pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC), medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administra­tion (FDA) approved sonidegib, a smoothened (SMO) antagonist, for treatment of advanced BCC (aBCC) after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mecha­nism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles)? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)1645-1653
Number of pages9
JournalOncoTargets and Therapy
Volume10
DOIs
StatePublished - Mar 16 2017

Fingerprint

Clinical Pharmacology
Basal Cell Carcinoma
United States Food and Drug Administration
HhAntag691
Phase II Clinical Trials
Medulloblastoma
Critical Pathways
Gastrointestinal Neoplasms
Metabolome
Embryonic Development
LDE225
Cell Differentiation
Neoplasms
Stem Cells
Maintenance
Clinical Trials
Safety

Keywords

  • Basal cell carcinoma
  • Cancer
  • Hedgehog
  • Inhibitor
  • Smoothened
  • Sonidegib

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

Cite this

Sonidegib : Mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas. / Jain, Sachin; Song, Ruolan; Xie, Jingwu.

In: OncoTargets and Therapy, Vol. 10, 16.03.2017, p. 1645-1653.

Research output: Contribution to journalReview article

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