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靶向癌症中的Hippo信号通路:TEAD抑制剂的类效应导致肾毒性?

Targeting the Hippo pathway in cancer: kidney toxicity as a class effect of TEAD inhibitors?

作者信息

Paul Sayantanee, Sims Jessica, Pham Trang, Dey Anwesha

机构信息

Department of Discovery Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080.

Department of Safety Assessment, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080.

出版信息

Trends Cancer. 2025 Jan;11(1):25-36. doi: 10.1016/j.trecan.2024.10.004. Epub 2024 Nov 8.

DOI:10.1016/j.trecan.2024.10.004
PMID:39521692
Abstract

The Hippo pathway has emerged as a critical player in both cancers and targeted therapy resistance. Recent drug discovery efforts have led to the development of TEAD inhibitors, several of which have already progressed to the clinic. To truly leverage their potential as anticancer therapeutics, safety considerations, particularly in regard to the kidney, warrant additional investigation. This review explores the Hippo pathway's role in cancers, its therapeutic potential, role in kidney development, and the need to evaluate the best strategies to translate its clinical application for long-term patient benefit.

摘要

河马通路已成为癌症和靶向治疗耐药性中的关键因素。最近的药物研发工作已促成TEAD抑制剂的开发,其中几种已进入临床试验阶段。为了真正发挥其作为抗癌治疗药物的潜力,安全性考量,尤其是肾脏方面的安全性,需要进一步研究。本综述探讨了河马通路在癌症中的作用、其治疗潜力、在肾脏发育中的作用,以及评估将其临床应用转化为长期患者获益的最佳策略的必要性。

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Targeting the Hippo pathway in cancer: kidney toxicity as a class effect of TEAD inhibitors?靶向癌症中的Hippo信号通路:TEAD抑制剂的类效应导致肾毒性?
Trends Cancer. 2025 Jan;11(1):25-36. doi: 10.1016/j.trecan.2024.10.004. Epub 2024 Nov 8.
2
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Cooperation between the Hippo and MAPK pathway activation drives acquired resistance to TEAD inhibition.Hippo信号通路与MAPK信号通路激活之间的协同作用驱动了对TEAD抑制的获得性耐药。
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引用本文的文献

1
Pipeline to evaluate YAP-TEAD inhibitors indicates TEAD inhibition represses -mutant mesothelioma.评估YAP-TEAD抑制剂的流程表明,TEAD抑制可抑制-突变型间皮瘤。
Life Sci Alliance. 2025 Jul 31;8(10). doi: 10.26508/lsa.202503241. Print 2025 Oct.
2
Targeting the Hippo pathway in cancer.靶向癌症中的Hippo信号通路。
Nat Rev Drug Discov. 2025 Jun 30. doi: 10.1038/s41573-025-01234-0.
3
Targeting YAP/TAZ-TEAD signaling as a therapeutic approach in head and neck squamous cell carcinoma.靶向YAP/TAZ-TEAD信号传导作为头颈鳞状细胞癌的一种治疗方法。
Cancer Lett. 2025 Mar 1;612:217467. doi: 10.1016/j.canlet.2025.217467. Epub 2025 Jan 16.