DR-07TARGETING EGFR-VIII WITH DICHLOROACETATE IN TEMOZOLOMIDE RESISTANT GLIOBLASTOMA MODELS

摘要: Epidermal growth factor receptor (EGFR) gene amplification and its subsequent over-expression is the most frequent genetic alteration associated with glioblastoma (GBM) approximating 40%. EGFR accompanied by a rearrangement that overexpresses variant III (EGFRvIII) characterized an in-frame deletion of 801 bp coding sequence from exons 2-7. Our in vitro preliminary studies conducted using U373 cell lines stably expressing EGFRvIII (U373vIII) conferred increased proliferation invasiveness when compared to control. Temozolomide (TMZ) resistance this context well-known concept, where high initial response met eventual failure tumor propagation. We thus generated aggressive TMZ model for U373vIII cells (U373vIII-TMZ-R) continual exposure 150uM 6 months. After phase death majority prolonged lag replication, surviving U373vIII-TMZ-R colonies showed identical morphology potential parent U373vIII. This resulted line mimicking actual recurrent GBM. have previously shown dichloroacetic acid (DCA) reduces expression GBMs. Since displays phenotype yet remains specific, we hypothesize studying DCA alone or combination dasatinib, inhibitor subcellular translocation, lines. By more accurately depicting status GBM at time recurrence after standard care chemotherapy treatment, investigation will augment possibly redefine our current understanding mechanisms establish novel methods circumventing pervasive phenomena.