Bulent Ozpolat
University of Texas, USA
Title: Development of novel targeted therapies for triple negative breast cancer: Targeting EF2-kinase
Biography
Biography: Bulent Ozpolat
Abstract
Triple-negative breast cancer refers to any breast cancer which is clinically characterized as more aggressive and less responsive to standard treatments, and is associated with poor overall patient prognosis. Th erefore, there is an urgent need to develop eff ective and safe therapies against triple negative breast cancer due to poor prognosis and lack of targeted therapies. Recently, we found that EF2-Kinase (EF2K) is signifi cantly overexpressed in breast cancer cell lines compared with normal breast epithelium and its expression is associated with poor patient overall survival. However, its regulation and the
role in breast cancer progression and tumorigenesis are not known. We demonstrated, for the fi rst time, that inhibition of EF2K blocked proliferation, colony formation and invasion and tumorigenesis of TNBC tumors. We also discovered that FOXM1 and a microRNA directly binds and regulates EF2K gene expression and targeting of these molecules recapitulates the eff ects of
EF2K targeting inhibit proliferation, invasion migration and tumor growth in TNBC models. We demonstrated blocked tumor growth tumor xenograft s and signifi cantly enhanced the in vivo effi cacy of chemotherapy. Inhibition of FOXM1-miRNA/eEF2K axis signifi cantly reduced Src/Fak/Paxillin, IGF-1R, PI3K/Akt/mTOR, cyclinD1, c-myc, HIF1 alpha and VEGF and induced
significant apoptosis in tumors. Overall, our studies suggest that EF2-Kinase plays an important role in TNBC tumorigenesis and progression and EF2K targeted therapies provide the proof of concept for translation into Phase-I clinical trials in patients.
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