title: Targeting the hedgehog pathway to treat basal cell carcinoma.
abstract: 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.
authors: Department of Radiology, University Hospital, Brussels, Belgium.
authors: Pieter
authors: P
authors: Geeraert
authors: Jonathan S
authors: JS
authors: Williams
authors: Isaac
authors: I
authors: Brownell
mesh_terms: D000813:Anilides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001478:Basal Cell Nevus Syndrome / Q000188:drug therapy* / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000473:pathology; D017277:Drug Approval; D015195:Drug Design; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines