Beckman Research Institute, City of Hope, Duarte, CA, USA.
Handb Exp Pharmacol. 2021;269:383-422. doi: 10.1007/164_2021_523.
WNT/β-catenin signaling plays fundamental roles in numerous developmental processes and in adult tissue homeostasis and repair after injury, by controlling cellular self-renewal, activation, division, differentiation, movement, genetic stability, and apoptosis. As such, it comes as no surprise that dysregulation of WNT/β-catenin signaling is associated with various diseases, including cancer, fibrosis, neurodegeneration, etc. Although multiple agents that specifically target the WNT/β-catenin signaling pathway have been studied preclinically and a number have entered clinical trials, none has been approved by the FDA to date. In this chapter, we provide our insights as to the reason(s) it has been so difficult to safely pharmacologically target the WNT/β-catenin signaling pathway and discuss the significant efforts undertaken towards this goal.
WNT/β-catenin 信号通路在许多发育过程以及成年组织损伤后的稳态和修复中发挥着基本作用，通过控制细胞的自我更新、激活、分裂、分化、迁移、遗传稳定性和细胞凋亡来发挥作用。因此，WNT/β-catenin 信号通路的失调与各种疾病有关，包括癌症、纤维化、神经退行性疾病等，这并不奇怪。尽管已经有多种专门针对 WNT/β-catenin 信号通路的药物在临床前进行了研究，并且其中一些已经进入临床试验，但迄今为止，没有一种药物被 FDA 批准。在本章中，我们将提供我们对为什么安全地用药物靶向 WNT/β-catenin 信号通路如此困难的见解，并讨论为此目的所做的重要努力。
