This review talks about how a pair of proteins called YAP/TAZ team up with TEAD to drive cancer growth and how scientists are trying to block that partnership with new drugs, but it doesn’t give any tips you can use at home for health or performance.

The Hippo signaling pathway, an evolutionarily conserved system, plays a critical role in regulating key biological processes. Dysregulation of this pathway has been implicated in wide range of human cancers. The transcription coactivators YAP (Yes-associated protein) and its paralog TAZ (transcriptional coactivator with PDZ-binding motif),as the main effector of Hippo signaling, predominantly interact with TEAD transcription factors to drive gene expression that promotes oncogenic processes. Given the pivotal role of the YAP/TAZ-TEAD axis in cancer progression, targeting these proteins and inhibiting YAP/TAZ-TEAD interaction represent promising therapeutic strategies. Recent breakthroughs, including the identification of the druggable TEAD palmitoylation pocket and the development of PROTAC technology, have accelerated the efforts to target YAP/TAZ-TEAD and curtail their oncogenic activities. Notably, several pioneer TEAD inhibitors and YAP/TAZ-TEAD protein-protein interaction inhibitors have progressed into clinical trials. This review dissects the structure and mechanistic details of YAP/TAZ-TEAD interactions and provides a comprehensive overview of recent advances in chemical compounds targeting YAP, TAZ, TEAD, and YAP/TAZ-TEAD PPI, highlighting the therapeutic potential of YAP/TAZ-TEAD axis as target for precision cancer therapy.