Advances of targeting the YAP/TAZ-TEAD complex in the hippo pathway for the treatment of cancers

Eur J Med Chem. 2022 Dec 15:244:114847. doi: 10.1016/j.ejmech.2022.114847. Epub 2022 Oct 13.

Abstract

The Hippo pathway is an evolutionarily conserved signaling pathway that plays critical roles in the tumorigenesis and progression of breast cancer, oral cancer, rectal cancer, colloid cancer, and so on. YAP/TAZ-TEAD complex is a key knot in the Hippo pathway regulating cell proliferation and stem cell functions. Activation or overexpression of this complex has been proved to lead to cell transformation, proliferation and eventually cancerization. In this review, the association between the alterations of hippo pathway and tumorigenesis of various cancer had been elucidated. The structural basis of YAP/TAZ-TEAD complex is analyzed, and the targeting inhibitors are summarized within the medicinal chemistry classification. Moreover, we have also discussed the clinical status and current challenges of these drug candidates, and provide guidance for the future development of inhibitors targeting this pathway, especially YAP/TAZ-TEAD complex.

Keywords: Cancers; Hippo pathway; Palmitoyl pocket; Targeting inhibitors; YAP/TAZ-TEAD complex.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Carcinogenesis* / drug effects
  • Carcinogenesis* / metabolism
  • Hippo Signaling Pathway* / drug effects
  • Humans
  • Multiprotein Complexes / antagonists & inhibitors
  • Multiprotein Complexes / chemistry
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Protein Conformation
  • TEA Domain Transcription Factors* / antagonists & inhibitors
  • TEA Domain Transcription Factors* / chemistry
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins* / antagonists & inhibitors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins* / chemistry
  • YAP-Signaling Proteins* / antagonists & inhibitors
  • YAP-Signaling Proteins* / chemistry

Substances

  • YAP-Signaling Proteins
  • Antineoplastic Agents
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • TEA Domain Transcription Factors
  • Multiprotein Complexes