Targeting the hedgehog pathway to treat basal cell carcinoma
Geeraert, P.; Williams, J.S.; Brownell, I.
Journal of Drugs in Dermatology Jdd 12(5): 519-523
2013
ISSN/ISBN: 1545-9616 PMID: 23652945 Document Number: 15157
The discovery of mutations that activate hedgehog (Hh) signaling in basal cell carcinoma (BCC) and other cancers has spurred the development of small molecule inhibitors that target the Hh pathway. High-throughput screens have identified a number of drug candidates that antagonize smoothened (SMO), an essential protein in the Hh signaling pathway. Clinical studies of the oral SMO inhibitor vismodegib (GDC-0449) in patients with inoperable or metastatic BCC have led to its recent approval by the US Food and Drug Administration. This review aims to give the clinician an overview of vismodegib and other Hh pathway inhibitors in the treatment of patients with advanced BCC and basal cell nevus syndrome. Issues of drug mechanism, efficacy, safety, tolerability, and tumor resistance are addressed.
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