Pre-clinical Activity of Targeting the PI3K/Akt/mTOR Pathway in Burkitt Lymphoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 May 19

PMID 29774105

Citations 8

Authors

Maria Bhatti

Thomas Ippolito

Cory Mavis

Juan Gu

Mitchell S Cairo

Megan S Lim

Francisco Hernandez-Ilizaliturri

Matthew J Barth

Affiliations

Soon will be listed here.

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 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.

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