YAP/TAZ Signaling and Resistance to Cancer Therapy

Trends Cancer. 2019 May;5(5):283-296. doi: 10.1016/j.trecan.2019.02.010. Epub 2019 Mar 27.

Abstract

Drug resistance is a major challenge in cancer treatment. Emerging evidence indicates that deregulation of YAP/TAZ signaling may be a major mechanism of intrinsic and acquired resistance to various targeted and chemotherapies. Moreover, YAP/TAZ-mediated expression of PD-L1 and multiple cytokines is pivotal for tumor immune evasion. While direct inhibitors of YAP/TAZ are still under development, FDA-approved drugs that indirectly block YAP/TAZ activation or critical downstream targets of YAP/TAZ have shown promise in the clinic in reducing therapy resistance. Finally, BET inhibitors, which reportedly block YAP/TAZ-mediated transcription, present another potential venue to overcome YAP/TAZ-induced drug resistance.

Keywords: Cancer therapy resistance; Hippo pathway; TAZ; YAP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acyltransferases
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor
  • Cell Cycle Proteins / metabolism*
  • Drug Resistance, Neoplasm* / genetics
  • Humans
  • Immunohistochemistry
  • Molecular Targeted Therapy
  • Neoplasms / etiology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Signal Transduction*
  • Transcription Factors / metabolism*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Transcription Factors
  • YY1AP1 protein, human
  • Acyltransferases
  • TAFAZZIN protein, human