Abidi Afroz
Department of Pharmacology, Subharti Medical College, Meerut, Uttar Pradesh, India.
Indian J Pharmacol. 2014 Jan-Feb;46(1):3-12. doi: 10.4103/0253-7613.124884.
The Hedgehog signaling pathway is one of the major regulators of cell growth and differentiation during embryogenesis and early development. It is mostly quiescent in adults but inappropriate mutation or deregulation of the pathway is involved in the development of cancers. Therefore; recently it has been recognized as a novel therapeutic target in cancers. Basal cell carcinomas (BCC) and medulloblastomas are the two most common cancers identified with mutations in components of the hedgehog pathway. The discovery of targeted Hedgehog pathway inhibitors has shown promising results in clinical trials, several of which are still undergoing clinical evaluation. Vismodegib (GDC-0449), an oral hedgehog signaling pathway inhibitor has reached the farthest in clinical development. Initial clinical trials in basal cell carcinoma and medulloblastoma have shown good efficacy and safety and hence were approved by U.S. FDA for use in advanced basal cell carcinomas. This review highlights the molecular basis and the current knowledge of hedgehog pathway activation in different types of human cancers as well as the present and future prospects of the novel drug vismodegib.
刺猬信号通路是胚胎发生和早期发育过程中细胞生长和分化的主要调节因子之一。在成体中它大多处于静止状态，但该信号通路的不适当突变或失调与癌症的发生有关。因此，最近它被认为是癌症的一个新的治疗靶点。基底细胞癌（BCC）和髓母细胞瘤是两种最常见的、与刺猬信号通路成分突变有关的癌症。靶向刺猬信号通路抑制剂的发现已在临床试验中显示出有前景的结果，其中一些仍在进行临床评估。维莫德吉（GDC - 0449），一种口服的刺猬信号通路抑制剂，在临床开发中进展最远。基底细胞癌和髓母细胞瘤的初步临床试验已显示出良好的疗效和安全性，因此被美国食品药品监督管理局（FDA）批准用于晚期基底细胞癌。本综述重点介绍了刺猬信号通路在不同类型人类癌症中激活的分子基础和当前认知，以及新型药物维莫德吉的现状和未来前景。
