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International Conference on Neuro Oncology and Brain Tumor

Brisbane, Australia

Rheal A. Towner,

Oklahoma Medical Research Foundation, USA

Title: OKN-007 is a New Therapeutic Approach for Adult and Pediatric Glioblastomas

Biography

Biography: Rheal A. Towner,

Abstract

OKN-007 is a New Therapeutic Approach for Adult and Pediatric Glioblastomas: Adult glioblastomas (aGBM) are the most common malignant primary brain tumors worldwide. Pediatric glioblastomas (pGBM) are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. OKN-007 is a novel nitrone-based compound that has anti-cancer activity in both adult and pediatric GBM. Magnetic resonance imaging (MRI) techniques were used to assess the efficacy of OKN-007 in orthotopic aGBM rat (C6, F98) and mouse (GL261) models, as well as human xenograft aGBM rat (U87) and pGBM mouse (IC-3752GBM) models. OKN-007 was found to significantly decrease tumor volumes and increase animal survival in OKN-007-treated rodents compared to untreated animals, and increase diffusion and perfusion rates. OKN-007 also significantly reduced lipid tumor metabolism, and as significantly decreased tumor cell proliferation and microvessel density. Immunohistochemistry support data was also obtained for cell proliferation and tumor growth signaling. Microarray data indicates that OKN-007 in aGBM model is centrally controlled by the TGFβ1 (transforming growth factor β1) pathway. For pGBM, in relationship to the PDGFRα (platelet-derived growth factor receptor-α) pathway, OKN-007 was able to significantly decrease PDGFR-α and SULF2 immunoexpression, and significantly increase decorin expression. This study indicates that OKN-007 may be an effective anti-cancer agent for adult or pediatric patients with aGBMs or pGBMs, respectively by inhibiting cell proliferation and angiogenesis, possibly via the TGFβ1 and/or PDGFRα pathways, and could be considered as an additional therapy for both adult or pediatric brain tumor patients.