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Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

Authors Jain S, Song R, Xie J

Received 22 December 2016

Accepted for publication 13 February 2017

Published 16 March 2017 Volume 2017:10 Pages 1645—1653

DOI https://doi.org/10.2147/OTT.S130910

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr William Cho

Sachin Jain,1 Ruolan Song,2 Jingwu Xie2

1Indiana University School of Medicine, 2Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN, USA

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.

Keywords: Hedgehog, smoothened, inhibitor, cancer, basal cell carcinoma, sonidegib

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Targeting hedgehog signaling in cancer: research and clinical developments

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