Geeraert Pieter, Williams Jonathan S, Brownell Isaac
Department of Radiology, University Hospital, Brussels, Belgium.
J Drugs Dermatol. 2013 May;12(5):519-23.
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.
在基底细胞癌（BCC）和其他癌症中发现激活刺猬信号通路（Hh）的突变，促使了针对Hh通路的小分子抑制剂的研发。高通量筛选已鉴定出多种可拮抗Hh信号通路中必需蛋白——平滑肌瘤（SMO）的候选药物。口服SMO抑制剂维莫德吉（GDC-0449）用于无法手术或转移性BCC患者的临床研究，使其近期获得了美国食品药品监督管理局的批准。本综述旨在为临床医生概述维莫德吉和其他Hh通路抑制剂在晚期BCC和基底细胞痣综合征患者治疗中的应用。文中讨论了药物作用机制、疗效、安全性、耐受性和肿瘤耐药性等问题。
