Pre-clinical activity of targeting the PI3K/Akt/mTOR pathway in Burkitt lymphoma

Oncotarget
Maria BhattiMatthew J Barth

Abstract

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 ...Continue Reading

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Citations

Feb 20, 2019·Genes, Chromosomes & Cancer·Dominique PentherFabrice Jardin
Apr 8, 2020·Leukemia & Lymphoma·Adam S Zayac, Adam J Olszewski
Jul 21, 2020·Expert Opinion on Pharmacotherapy·Piotr Smolewski, Dominika Rydygier
Aug 7, 2020·Journal of the National Comprehensive Cancer Network : JNCCN·Paul D Harker-MurrayMatthew J Barth
Feb 8, 2019·British Journal of Haematology·Monika L Metzger, Christine Mauz-Körholz
Feb 1, 2019·British Journal of Haematology·Matthew J Barth, Veronique Minard-Colin

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Methods Mentioned

BETA
transgenic
flow cytometry
Assay
immunoprecipitation
electrophoresis

Software Mentioned

CalcuSyn
Mod Fit LT

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