Abstract 3281: Oklahoma Nitrone-007: A novel compound for treating pediatric glioblastoma

Abstract

Abstract Brain tumors are the most common solid tumor in children, and despite current treatment options including surgical resection, chemotherapy, and radiation for pediatric high-grade gliomas, survival in these patients remains very poor. This research represents promising pre-clinical data of a novel compound, OKN-007 (OKlahoma Nitrone 007, a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)), as a new clinical therapy for pediatric high-grade gliomas (pHGGs). The objective is to establish if pHGGs, which are often hard to surgically resect, can be treated with OKN-007, either as a single agent or in combination with currently used chemotherapeutic agents. OKN-007 may be an ideal candidate that can have an anti-cancer effect on pHGG cells, due to its multiple anti-cancer effects, including induction of apoptosis, and inhibition of cell proliferation and angiogenesis, and may play an important role in the anti-cancer activity against pHGGs. Morphological magnetic resonance imaging (MRI) of xenograft nude athymic and SCID mice injected with pHGG cells TCCC3752 and KNS42 is used in this study to assess brain tumor volumes for response to therapy. Preliminary data regarding the regression of pHGGs in mice following treatment with OKN-007 is presented. Mean animal survival was found to be significantly increased with OKN-007 treatment in responsive animals compared to an untreated group, p<0.05. Immunohistochemistry and microarray will be used to assess levels of angiogenic (VEGF (vascular endothelial growth factor), HIF-1α (hypoxia inducible factor-1α), MVD (microvessel density)), cell differentiation (CAIX (carbonic anhydrase IX)), cell proliferation (Glut-1 (glucose transporter 1), MIB-1), apoptosis (cleaved caspase 3) markers and assess inhibition of TGFB and PDGFR complexes and downstream pathways, which are overexpressed in tumors and thought to play a role in oncogenesis and progression. OKN-007 is currently an investigational drug undergoing clinical trial evaluation for recurrent gliomas in adult patients but will still require FDA approval for use in pediatric glioma patients. An outcome of the proposed research is to incorporate the pre-clinical data in an IND application to the FDA in order to translate this research to the clinic and benefit children with pHGGs. Citation Format: Samantha Mallory, Rene McNall-Knapp, Patricia Coutinho deSouza, Kar-Ming Fung, Debra Saunders, Nataliya Smith, Shanna Smartwood, Rheal Towner. Oklahoma Nitrone-007: A novel compound for treating pediatric glioblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3281. doi:10.1158/1538-7445.AM2015-3281