Evaluating the evidence for targeting FOXO3a in breast cancer: a systematic review

Simon Taylor, Matthew Lam, Chathyan Pararasa, James E.P. Brown, Amtul R. Carmichael, Helen R. Griffiths

Research output: Contribution to journalArticle

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. Discussion: 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.

LanguageEnglish
Number of pages9
JournalCancer Cell International
Volume15
Issue number1
DOIs
Publication statusPublished - 2015

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Triple Negative Breast Neoplasms
Breast Neoplasms
Intercellular Signaling Peptides and Proteins
Glycolysis
Apoptosis
Phosphatidylinositol 3-Kinase
Pharmaceutical Preparations
Growth Factor Receptors
Cell Cycle Checkpoints
MicroRNAs
Epidermal Growth Factor Receptor
Estrogen Receptors
Progesterone
Signal Transduction
Neoplasms
Estrogens
Research Design
Therapeutics
Enzymes
Growth

Bibliographical note

© 2015 Taylor et al.; licensee BioMed Central.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Keywords

  • Apoptosis
  • Glycolysis
  • Metabolism
  • Oxidative stress
  • Phosphatidylinositol 3-kinase
  • Triple negative breast cancer

Cite this

Taylor, Simon ; Lam, Matthew ; Pararasa, Chathyan ; Brown, James E.P. ; Carmichael, Amtul R. ; Griffiths, Helen R. / Evaluating the evidence for targeting FOXO3a in breast cancer : a systematic review. In: Cancer Cell International. 2015 ; Vol. 15, No. 1.
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Evaluating the evidence for targeting FOXO3a in breast cancer : a systematic review. / Taylor, Simon; Lam, Matthew; Pararasa, Chathyan; Brown, James E.P.; Carmichael, Amtul R.; Griffiths, Helen R.

In: Cancer Cell International, Vol. 15, No. 1, 2015.

Research output: Contribution to journalArticle

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AU - Carmichael, Amtul R.

AU - Griffiths, Helen R.

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