Xie Jingwu
Department of Pharmacology and Toxicology, Sealy Center for Cancer Cell Biology, University of Texas at Galveston, Galveston, Texas 77555-1048, USA.
Acta Biochim Biophys Sin (Shanghai). 2008 Jul;40(7):670-80. doi: 10.1111/j.1745-7270.2008.00431.x.
The hedgehog (Hh) pathway, initially discovered in Drosophila by two Nobel laureates, Dr. Eric Wieschaus and Dr. Christiane Nusslein-Volhard, is a major regulator for cell differentiation, tissue polarity and cell proliferation. Studies from many laboratories, including ours, reveal activation of this pathway in most basal cell carcinomas and in approximately 30% of extracutaneous human cancers, including medulloblastomas, gastrointestinal, lung, breast and prostate cancers. Thus, it is believed that targeted inhibition of Hh signaling may be effective in treating and preventing many types of human cancers. Even more exciting is the discovery and synthesis of specific signaling antagonists for the Hh pathway, which have significant clinical implications in novel cancer therapeutics. This review discusses the major advances in the current understanding of Hh signaling activation in different types of human cancers, the molecular basis of Hh signaling activation, the major antagonists for Hh signaling inhibition and their potential clinical application in human cancer therapy.
刺猬（Hh）信号通路最初由两位诺贝尔奖获得者埃里克·维绍斯博士和克里斯蒂iane·努斯莱因 - 福尔哈德博士在果蝇中发现，是细胞分化、组织极性和细胞增殖的主要调节因子。包括我们实验室在内的许多实验室的研究表明，这条信号通路在大多数基底细胞癌以及约30%的皮肤外人类癌症中被激活，这些癌症包括髓母细胞瘤、胃肠道癌、肺癌、乳腺癌和前列腺癌。因此，人们认为靶向抑制Hh信号可能对治疗和预防多种类型的人类癌症有效。更令人兴奋的是Hh信号通路特异性信号拮抗剂的发现和合成，这在新型癌症治疗中具有重要的临床意义。本综述讨论了目前对不同类型人类癌症中Hh信号激活的理解、Hh信号激活的分子基础、Hh信号抑制的主要拮抗剂及其在人类癌症治疗中的潜在临床应用的主要进展。
