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

Taylor S, Lam M, Pararasa C, Brown JE, Carmichael AR, Griffiths HR - Cancer Cell Int. (2015)

Bottom Line: 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.The identification of microRNA that regulate FOXO3a directly suggest that it offers a tangible therapeutic target that merits wider evaluation.

View Article: PubMed Central - PubMed

Affiliation: Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET UK.

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.

No MeSH data available.


Related in: MedlinePlus

Flowchart showing the retrieval and review of literature according to systematic criteria.
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Fig2: Flowchart showing the retrieval and review of literature according to systematic criteria.

Mentions: The systematic search for relevant articles initially retrieved 148 articles. The 51 articles that met the inclusion criteria were then analysed and categorised according to the drug target (extracellular receptor; PI3k; AKT; FOXO3a), and assessed for dependency on FOXO3a activity. Twenty articles met these conditions and have been analysed here (FigureĀ 2).Figure 2


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

Taylor S, Lam M, Pararasa C, Brown JE, Carmichael AR, Griffiths HR - Cancer Cell Int. (2015)

Flowchart showing the retrieval and review of literature according to systematic criteria.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4325954&req=5

Fig2: Flowchart showing the retrieval and review of literature according to systematic criteria.
Mentions: The systematic search for relevant articles initially retrieved 148 articles. The 51 articles that met the inclusion criteria were then analysed and categorised according to the drug target (extracellular receptor; PI3k; AKT; FOXO3a), and assessed for dependency on FOXO3a activity. Twenty articles met these conditions and have been analysed here (FigureĀ 2).Figure 2

Bottom Line: 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.The identification of microRNA that regulate FOXO3a directly suggest that it offers a tangible therapeutic target that merits wider evaluation.

View Article: PubMed Central - PubMed

Affiliation: Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET UK.

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.

No MeSH data available.


Related in: MedlinePlus