REVIEW article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Targeting TEAD in Cancer
Provisionally accepted
- Georgetown University Medical Center, Washington D.C., United States
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The Hippo pathway is dysregulated in many cancers, leading to pro-oncogenic effects. The transcription factor TEAD plays a critical role in early development, tissue homeostasis, and cell proliferation, and it binds to the downstream Hippo pathway co-activators YAP and TAZ. Numerous studies have examined the roles of YAP/TAZ and TEAD in cancer, with their activity frequently linked to poor clinical prognosis. This review discusses how targeting TEAD interactions with coregulators—most notably YAP and TAZ—represents a promising therapeutic strategy in oncology. Several pharmacological agents have been developed to disrupt the YAP/TAZ–TEAD complex, and many are currently being evaluated for clinical applicability across diverse cancer types. We review current knowledge on the structure and homology of TEAD, emphasizing the protein–protein interfaces that mediate binding to YAP/TAZ and other cofactors. Advances in understanding the YAP/TAZ–TEAD complex have informed the development of diverse strategies to inhibit downstream transcription of key oncogenic target genes. Finally, we highlight TEAD inhibitors currently in clinical trials, outlining their mechanisms of action, associated adverse effects, and potential impact on the future therapeutic landscape.
Keywords: TEAD family, Yap (Hippo) signaling, TAZ (Hippo) signaling, TEAD inhibitors, YAP/TAZ TEAD Signaling
Received: 25 Aug 2025; Accepted: 29 Oct 2025.
Copyright: © 2025 Battina, Rahhal, Wellstein, Riegel and Sharif. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ghada Sharif, gms58@georgetown.edu
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