我们能否安全地靶向WNT信号通路？
Can we safely target the WNT pathway?
作者信息
Kahn Michael
机构信息
USC Norris Comprehensive Cancer Center, USC Center for Molecular Pathways and Drug Discovery, University of Southern California, Los Angeles, California 90033, USA.
出版信息
Nat Rev Drug Discov. 2014 Jul;13(7):513-32. doi: 10.1038/nrd4233.
Abstract
WNT-β-catenin signalling is involved in a multitude of developmental processes and the maintenance of adult tissue homeostasis by regulating cell proliferation, differentiation, migration, genetic stability and apoptosis, as well as by maintaining adult stem cells in a pluripotent state. Not surprisingly, aberrant regulation of this pathway is therefore associated with a variety of diseases, including cancer, fibrosis and neurodegeneration. Despite this knowledge, therapeutic agents specifically targeting the WNT pathway have only recently entered clinical trials and none has yet been approved. This Review examines the problems and potential solutions to this vexing situation and attempts to bring them into perspective.
摘要
WNT-β-连环蛋白信号通路通过调节细胞增殖、分化、迁移、遗传稳定性和凋亡，以及维持成体干细胞的多能状态，参与多种发育过程和成体组织稳态的维持。因此，毫不奇怪，该信号通路的异常调节与包括癌症、纤维化和神经退行性变在内的多种疾病相关。尽管有这些认识，但专门靶向WNT信号通路的治疗药物直到最近才进入临床试验，且尚无一种药物获批。本综述探讨了这一棘手情况所面临的问题和潜在解决方案，并试图对其进行全面审视。
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