OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins

Trends Mol Med. 2008 May;14(5):219-27. doi: 10.1016/j.molmed.2008.03.002. Epub 2008 Apr 9.


Forkhead transcription factors have a 'winged helix' domain and regulate processes that range from cell longevity to cell death. Of the mammalian forkhead family members in the O class, FoxO1, FoxO3a and FoxO4 can fill a crucial void for the treatment of disorders that include aging, cancer, diabetes, infertility, neurodegeneration and immune system dysfunction. Yet, observations that forkhead family members also can compromise clinical utility have fueled controversy and highlight the necessity to further outline the integrated cellular pathways governed by these transcription factors. Here we discuss recent advances that have elucidated the unique cellular pathways and clinical potential of targeting FoxO proteins to develop novel therapeutic strategies and avert potential pitfalls that might be closely intertwined with its benefits for patient care.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cell Movement
  • Drug Design
  • Forkhead Box Protein O1
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation
  • Humans
  • Models, Biological
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Oxidative Stress
  • Protein Transport
  • Signal Transduction
  • Transcription Factors / metabolism*


  • FOXO1 protein, human
  • FOXO3 protein, human
  • FOXO4 protein, human
  • Forkhead Box Protein O1
  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • Transcription Factors