Targeting Yes-Associated Protein (YAP)/Transcriptional Coactivators with PDZ-Binding Motif (TAZ)-Transcriptional Enhanced Associate Domain (TEAD) for Cancer and Regenerative Medicine.
The evolutionarily conserved Hippo signaling pathway is crucial for regulating organ size, tissue homeostasis, and regeneration. Mammalian Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) and its interaction with transcriptional enhanced associate domain 1-4 (TEAD1-4) are vital for transcriptional outputs linked to cell proliferation and apoptosis. Dysregulation of Hippo signaling is associated with various aspects of cancer biology. The convergence of the Hippo signaling network with diverse oncogenic pathways places it at the center of tumorigenic adaptation, maintenance of stemness, and the development of drug resistance. Modulating YAP/TAZ-TEAD signaling offers broad therapeutic potential, from cancer treatment to regenerative medicine. Several small-molecule TEAD inhibitors are at various stages of clinical development, with increasing efforts focused on monotherapy and combination therapies targeting YAP/TAZ hyperactivation caused by standard-of-care (SOC) drugs (best available disease-specific treatments used in clinics), particularly targeted therapies.