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Activation of the PI3K/mTOR/AKT Pathway and Survival in Solid Tumors: Systematic Review and Meta-Analysis

BACKGROUND: Aberrations in the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/AKT pathway are common in solid tumors. Numerous drugs have been developed to target different components of this pathway. However the prognostic value of these aberrations is unclear. METHODS: P...

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Autores principales: Ocana, Alberto, Vera-Badillo, Francisco, Al-Mubarak, Mustafa, Templeton, Arnoud J., Corrales-Sanchez, Verónica, Diez-Gonzalez, Laura, Cuenca-Lopez, María D., Seruga, Bostjan, Pandiella, Atanasio, Amir, Eitan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002433/
https://www.ncbi.nlm.nih.gov/pubmed/24777052
http://dx.doi.org/10.1371/journal.pone.0095219
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author Ocana, Alberto
Vera-Badillo, Francisco
Al-Mubarak, Mustafa
Templeton, Arnoud J.
Corrales-Sanchez, Verónica
Diez-Gonzalez, Laura
Cuenca-Lopez, María D.
Seruga, Bostjan
Pandiella, Atanasio
Amir, Eitan
author_facet Ocana, Alberto
Vera-Badillo, Francisco
Al-Mubarak, Mustafa
Templeton, Arnoud J.
Corrales-Sanchez, Verónica
Diez-Gonzalez, Laura
Cuenca-Lopez, María D.
Seruga, Bostjan
Pandiella, Atanasio
Amir, Eitan
author_sort Ocana, Alberto
collection PubMed
description BACKGROUND: Aberrations in the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/AKT pathway are common in solid tumors. Numerous drugs have been developed to target different components of this pathway. However the prognostic value of these aberrations is unclear. METHODS: PubMed was searched for studies evaluating the association between activation of the PI3K/mTOR/AKT pathway (defined as PI3K mutation [PIK3CA], lack of phosphatase and tensin homolog [PTEN] expression by immunohistochemistry or western-blot or increased expression/activation of downstream components of the pathway by immunohistochemistry) with overall survival (OS) in solid tumors. Published data were extracted and computed into odds ratios (OR) for death at 5 years. Data were pooled using the Mantel-Haenszel random-effect model. RESULTS: Analysis included 17 studies. Activation of the PI3K/mTOR/AKT pathway was associated with significantly worse 5-year survival (OR:2.12, 95% confidence intervals 1.42–3.16, p<0.001). Loss of PTEN expression and increased expression/activation of downstream components were associated with worse survival. No association between PIK3CA mutations and survival was observed. Differences between methods for assessing activation of the PI3K/mTOR/AKT pathway were statistically significant (p = 0.04). There was no difference in the effect of up-regulation of the pathway on survival between different cancer sites (p = 0.13). CONCLUSION: Activation of the PI3K/AKT/mTOR pathway, especially if measured by loss of PTEN expression or increased expression/activation of downstream components is associated with poor survival. PIK3CA mutational status is not associated with adverse outcome, challenging its value as a biomarker of patient outcome or as a stratification factor for patients treated with agents acting on the PI3K/AKT/mTOR pathway.
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spelling pubmed-40024332014-05-02 Activation of the PI3K/mTOR/AKT Pathway and Survival in Solid Tumors: Systematic Review and Meta-Analysis Ocana, Alberto Vera-Badillo, Francisco Al-Mubarak, Mustafa Templeton, Arnoud J. Corrales-Sanchez, Verónica Diez-Gonzalez, Laura Cuenca-Lopez, María D. Seruga, Bostjan Pandiella, Atanasio Amir, Eitan PLoS One Research Article BACKGROUND: Aberrations in the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/AKT pathway are common in solid tumors. Numerous drugs have been developed to target different components of this pathway. However the prognostic value of these aberrations is unclear. METHODS: PubMed was searched for studies evaluating the association between activation of the PI3K/mTOR/AKT pathway (defined as PI3K mutation [PIK3CA], lack of phosphatase and tensin homolog [PTEN] expression by immunohistochemistry or western-blot or increased expression/activation of downstream components of the pathway by immunohistochemistry) with overall survival (OS) in solid tumors. Published data were extracted and computed into odds ratios (OR) for death at 5 years. Data were pooled using the Mantel-Haenszel random-effect model. RESULTS: Analysis included 17 studies. Activation of the PI3K/mTOR/AKT pathway was associated with significantly worse 5-year survival (OR:2.12, 95% confidence intervals 1.42–3.16, p<0.001). Loss of PTEN expression and increased expression/activation of downstream components were associated with worse survival. No association between PIK3CA mutations and survival was observed. Differences between methods for assessing activation of the PI3K/mTOR/AKT pathway were statistically significant (p = 0.04). There was no difference in the effect of up-regulation of the pathway on survival between different cancer sites (p = 0.13). CONCLUSION: Activation of the PI3K/AKT/mTOR pathway, especially if measured by loss of PTEN expression or increased expression/activation of downstream components is associated with poor survival. PIK3CA mutational status is not associated with adverse outcome, challenging its value as a biomarker of patient outcome or as a stratification factor for patients treated with agents acting on the PI3K/AKT/mTOR pathway. Public Library of Science 2014-04-28 /pmc/articles/PMC4002433/ /pubmed/24777052 http://dx.doi.org/10.1371/journal.pone.0095219 Text en © 2014 Ocana et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ocana, Alberto
Vera-Badillo, Francisco
Al-Mubarak, Mustafa
Templeton, Arnoud J.
Corrales-Sanchez, Verónica
Diez-Gonzalez, Laura
Cuenca-Lopez, María D.
Seruga, Bostjan
Pandiella, Atanasio
Amir, Eitan
Activation of the PI3K/mTOR/AKT Pathway and Survival in Solid Tumors: Systematic Review and Meta-Analysis
title Activation of the PI3K/mTOR/AKT Pathway and Survival in Solid Tumors: Systematic Review and Meta-Analysis
title_full Activation of the PI3K/mTOR/AKT Pathway and Survival in Solid Tumors: Systematic Review and Meta-Analysis
title_fullStr Activation of the PI3K/mTOR/AKT Pathway and Survival in Solid Tumors: Systematic Review and Meta-Analysis
title_full_unstemmed Activation of the PI3K/mTOR/AKT Pathway and Survival in Solid Tumors: Systematic Review and Meta-Analysis
title_short Activation of the PI3K/mTOR/AKT Pathway and Survival in Solid Tumors: Systematic Review and Meta-Analysis
title_sort activation of the pi3k/mtor/akt pathway and survival in solid tumors: systematic review and meta-analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4002433/
https://www.ncbi.nlm.nih.gov/pubmed/24777052
http://dx.doi.org/10.1371/journal.pone.0095219
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