title: Evaluating the evidence for targeting FOXO3a in breast cancer: a systematic review.
abstract: BACKGROUND
  Tumour cells show greater dependency on glycolysis so providing a sufficient and rapid energy supply for fast growth. In many breast cancers, estrogen, progesterone and epidermal growth factor receptor-positive cells proliferate in response to growth factors and growth factor antagonists are a mainstay of treatment. However, triple negative breast cancer (TNBC) cells lack receptor expression, are frequently more aggressive and are resistant to growth factor inhibition. Downstream of growth factor receptors, signal transduction proceeds via phosphatidylinositol 3-kinase (PI3k), Akt and FOXO3a inhibition, the latter being partly responsible for coordinated increases in glycolysis and apoptosis resistance. FOXO3a may be an attractive therapeutic target for TNBC. Therefore we have undertaken a systematic review of FOXO3a as a target for breast cancer therapeutics.
  
  
  METHODS
  Articles from NCBI were retrieved systematically when reporting primary data about FOXO3a expression in breast cancer cells after cytotoxic drug treatment.
  
  
  RESULTS
  Increased FOXO3a expression is common following cytotoxic drug treatment and is associated with apoptosis and cell cycle arrest. There is some evidence that metabolic enzyme expression is also altered and that this effect is also elicited in TNBC cells. FOXO3a expression serves as a positive prognostic marker, especially in estrogen (ER) receptor positive cells.
  
  
  CONCLUSIONS
  FOXO3a is upregulated by a number of receptor-dependent and -independent anti-cancer drugs and associates with apoptosis. The identification of microRNA that regulate FOXO3a directly suggest that it offers a tangible therapeutic target that merits wider evaluation.
authors: Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET UK.
authors: Simon
authors: S
authors: Taylor
authors: Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET UK.
authors: Matthew
authors: M
authors: Lam
authors: Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET UK.
authors: Chathyan
authors: C
authors: Pararasa
authors: Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET UK.
authors: James Ep
authors: JE
authors: Brown
authors: Russells Hall Hospital, Dudley, DY1 2HQ UK.
authors: Amtul R
authors: AR
authors: Carmichael
authors: Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET UK.
authors: Helen R
authors: HR
authors: Griffiths
keywords: Apoptosis; Glycolysis; Metabolism; Oxidative stress; Phosphatidylinositol 3-kinase; Triple negative breast cancer