CSIG-21. EXPLORING THE PHENOTYPIC EFFECTS OF TOLL SIGNALING PATHWAYS IN TUMOR PROGRESSION IN EGFR-DRIVEN GLIOBLASTOMA MODELS

Abstract The treatment options for Glioblastoma (GBM) are currently limited to resection and chemotherapy approaches, but resistance is common in patients. There an urgent need further understanding of the underlying biology tumorigenesis order develop new options. Previous genomic work on GBMs has shown that epidermal growth factor receptor (EGFR) frequently amplified constitutively active GBM tumors. To discover factors contribute progression EGFR-driven GBMs, we used our Drosophila model which GBM-like glial neoplasia can be induced by glial-specific overexpression forms EGFR dp110, a subunit Phosphoinositide 3-kinase (PI3K), using UAS-GAL4 gene expression system. Using system, performed modifier screen searched genes pathways worsened or ‘enhanced’ when specifically overexpressed activated neoplastic glia. From screen, identified Toll pathway, activates NF-κB signaling pathway. Furthermore, pathway normally functions innate immune injury responses as well development cell proliferation. model, studying how its effectors, including NF-κB, enhanced cells. well-defined mouse genetic models human patient-derived models, examining whether regulatory mechanisms have uncovered function EGFR-mutant tumor stem cells promote resistance.