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Pre-clinical activity of targeting the PI3K/Akt/mTOR pathway in Burkitt lymphoma
Though outcomes for pediatric Burkitt lymphoma (BL) have improved significantly in recent decades with intensive multi-agent chemotherapy and the addition of rituximab, chemotherapy resistance remains a significant impediment to cure following relapse. Activation of the PI3K/AKT pathway has been imp...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955151/ https://www.ncbi.nlm.nih.gov/pubmed/29774105 http://dx.doi.org/10.18632/oncotarget.25072 |
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author | Bhatti, Maria Ippolito, Thomas Mavis, Cory Gu, Juan Cairo, Mitchell S. Lim, Megan S. Hernandez-Ilizaliturri, Francisco Barth, Matthew J. |
author_facet | Bhatti, Maria Ippolito, Thomas Mavis, Cory Gu, Juan Cairo, Mitchell S. Lim, Megan S. Hernandez-Ilizaliturri, Francisco Barth, Matthew J. |
author_sort | Bhatti, Maria |
collection | PubMed |
description | Though outcomes for pediatric Burkitt lymphoma (BL) have improved significantly in recent decades with intensive multi-agent chemotherapy and the addition of rituximab, chemotherapy resistance remains a significant impediment to cure following relapse. Activation of the PI3K/AKT pathway has been implicated in Burkitt lymphomagenesis and increased PI3K/AKT activation has been associated with worse outcomes in adults with aggressive B-cell non-Hodgkin lymphoma (B-NHL). Inhibitors of the PI3K/AKT pathway have been approved for the treatment of refractory indolent B-NHL and continue to be investigated for treatment of aggressive B-NHLs. We investigated the activation of the PI3K/AKT pathway in a cell line model of resistant BL and the ability to target this pathway with small molecule inhibitors in BL cell lines. We found that cell lines resistant to rituximab and chemotherapy exhibited increased activation of PI3K/AKT and that inhibition of AKT or PI3K results in in vitro anti-lymphoma activity. To investigate the role of PI3K/AKT activation on the efficacy of cytotoxic chemotherapy, we exposed cells to inhibitors in combination with chemotherapy and noted a synergistic increase in response to chemotherapy. Overall these findings highlight the role of PI3K/AKT in chemotherapy resistance in BL cells and may represent a tractable therapeutic target. |
format | Online Article Text |
id | pubmed-5955151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-59551512018-05-17 Pre-clinical activity of targeting the PI3K/Akt/mTOR pathway in Burkitt lymphoma Bhatti, Maria Ippolito, Thomas Mavis, Cory Gu, Juan Cairo, Mitchell S. Lim, Megan S. Hernandez-Ilizaliturri, Francisco Barth, Matthew J. Oncotarget Research Paper Though outcomes for pediatric Burkitt lymphoma (BL) have improved significantly in recent decades with intensive multi-agent chemotherapy and the addition of rituximab, chemotherapy resistance remains a significant impediment to cure following relapse. Activation of the PI3K/AKT pathway has been implicated in Burkitt lymphomagenesis and increased PI3K/AKT activation has been associated with worse outcomes in adults with aggressive B-cell non-Hodgkin lymphoma (B-NHL). Inhibitors of the PI3K/AKT pathway have been approved for the treatment of refractory indolent B-NHL and continue to be investigated for treatment of aggressive B-NHLs. We investigated the activation of the PI3K/AKT pathway in a cell line model of resistant BL and the ability to target this pathway with small molecule inhibitors in BL cell lines. We found that cell lines resistant to rituximab and chemotherapy exhibited increased activation of PI3K/AKT and that inhibition of AKT or PI3K results in in vitro anti-lymphoma activity. To investigate the role of PI3K/AKT activation on the efficacy of cytotoxic chemotherapy, we exposed cells to inhibitors in combination with chemotherapy and noted a synergistic increase in response to chemotherapy. Overall these findings highlight the role of PI3K/AKT in chemotherapy resistance in BL cells and may represent a tractable therapeutic target. Impact Journals LLC 2018-04-24 /pmc/articles/PMC5955151/ /pubmed/29774105 http://dx.doi.org/10.18632/oncotarget.25072 Text en Copyright: © 2018 Bhatti et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Bhatti, Maria Ippolito, Thomas Mavis, Cory Gu, Juan Cairo, Mitchell S. Lim, Megan S. Hernandez-Ilizaliturri, Francisco Barth, Matthew J. Pre-clinical activity of targeting the PI3K/Akt/mTOR pathway in Burkitt lymphoma |
title | Pre-clinical activity of targeting the PI3K/Akt/mTOR pathway in Burkitt lymphoma |
title_full | Pre-clinical activity of targeting the PI3K/Akt/mTOR pathway in Burkitt lymphoma |
title_fullStr | Pre-clinical activity of targeting the PI3K/Akt/mTOR pathway in Burkitt lymphoma |
title_full_unstemmed | Pre-clinical activity of targeting the PI3K/Akt/mTOR pathway in Burkitt lymphoma |
title_short | Pre-clinical activity of targeting the PI3K/Akt/mTOR pathway in Burkitt lymphoma |
title_sort | pre-clinical activity of targeting the pi3k/akt/mtor pathway in burkitt lymphoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955151/ https://www.ncbi.nlm.nih.gov/pubmed/29774105 http://dx.doi.org/10.18632/oncotarget.25072 |
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