The overall goal of this SPORE application is to develop more effective targeted molecular therapies and biomarkers for glioblastoma. The four proposed projects focus on 1) Overcoming resistance to VEGF inhibition by targeting Angiopoietin-2;2) Inhibiting the phosphatidylinositol 3-kinase (PI3 kinase) pathway;3) designing novel strategies for imaging and targeting IDH mutant gliomas;and 4) Increasing the radiosensitivity of glioblastomas by inhibiting the bHLH transcription factor Olig2. One ofthe innovative themes of this SPORE proposal is that biospecimens collected by the Pathology Core will be comprehensively moiecuiariy profiled using multiplexed technologies so projects may effectively evaluate the interaction of targeted therapies and their targets. The Pathology Core will support the goals of the SPORE by providing expert neuropathologic review, biospecimen banking and clinical trial support. In addition, the Pathology Core will be a centralized resource for clinically and moiecuiariy annotated glioblastoma tissues and primary glioblastoma cell cultures that will be essential to the success of the proposed projects. By centralizing these activities, the Pathology Core will ensure the safe and effective use of finite glioblastoma tissue resources without limiting the scope of the translational research planned in this proposal. The SPORE support, combined with significant institutional support for these goals, will ensure that over the next 5 years the Pathology Gore will provide the critical research infrastructure required for successful, collaborative translational research ofthe SPORE program.
The Pathology Core will combine neuropathology expertise and leading-edge molecular pathology assays to correlate glioblastoma patient profiles with response to targeted therapies. This work will aid development of new clinical diagnostic tests to identify patients likely to benefit from targeted therapy, while avoiding treatment and side effects in those least likely to respond.
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|Kloepper, Jonas; Riedemann, Lars; Amoozgar, Zohreh et al. (2016) Ang-2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival. Proc Natl Acad Sci U S A 113:4476-81|
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|Verreault, Maite; Schmitt, Charlotte; Goldwirt, Lauriane et al. (2016) Preclinical Efficacy of the MDM2 Inhibitor RG7112 in MDM2-Amplified and TP53 Wild-type Glioblastomas. Clin Cancer Res 22:1185-96|
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|Tateishi, Kensuke; Iafrate, A John; Ho, Quan et al. (2016) Myc-Driven Glycolysis Is a Therapeutic Target in Glioblastoma. Clin Cancer Res 22:4452-65|
|Cizmecioglu, Onur; Ni, Jing; Xie, Shaozhen et al. (2016) Rac1-mediated membrane raft localization of PI3K/p110Î² is required for its activation by GPCRs or PTEN loss. Elife 5:|
|Fathi, Amir T; Nahed, Brian V; Wander, Seth A et al. (2016) Elevation of Urinary 2-Hydroxyglutarate in IDH-Mutant Glioma. Oncologist 21:214-9|
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