Cancer Research Group, Faculty of Engineering and Applied Sciences, Universidad de Las Américas, Quito, Ecuador.
Faculty of Health Sciences and Medicine, Universidad de Extremadura, Mérida, Spain.
Nat Commun. 2024 Mar 27;15(1):2700. doi: 10.1038/s41467-024-46531-1.
Hyperactivation of YAP/TAZ, the Hippo pathway downstream effectors, is common in human cancer. The requirement of YAP/TAZ for cancer cell survival in preclinical models, prompted the development of pharmacological inhibitors that suppress their transcriptional activity. However, systemic YAP/TAZ inhibition may sometimes have unpredictable patient outcomes, with limited or even adverse effects because YAP/TAZ action is not simply tumor promoting but also tumor suppressive in some cell types. Here, we review the role of the Hippo pathway in distinct tumor cell populations, discuss the impact of inhibiting Hippo output on tumor growth, and examine current developments in YAP/TAZ inhibitors.
YAP/TAZ 的过激活是 Hippo 通路下游效应物的常见现象，存在于多种人类癌症中。在临床前模型中，YAP/TAZ 对于癌细胞存活的需求促使开发了抑制其转录活性的药理学抑制剂。然而，全身性 YAP/TAZ 抑制有时可能会导致不可预测的患者结果，其疗效有限，甚至出现不良反应，因为 YAP/TAZ 的作用不仅简单地促进肿瘤生长，而且在某些细胞类型中还具有肿瘤抑制作用。在这里，我们综述了 Hippo 通路在不同肿瘤细胞群体中的作用，讨论了抑制 Hippo 通路下游输出对肿瘤生长的影响，并研究了 YAP/TAZ 抑制剂的最新进展。
