The overall goal of the new P01 is to integrate advances in physiologic and metabolic imaging with tissue biomarkers in order to optimize the management of patients with glioblastoma. This will be achieved by characterizing the evolution of changes in imaging, genetic and epigenetic profiles from the time of initial presentation until presumed tumor progression. The information obtained will be applied to determine whether it is possible to tailor treatment strategies to individual patients and will be used in combination with hyperpolarized C-13 metabolic imaging to inform on the early response to therapeutic agents. The results of these studies will address critical challenges in the field of Neuro-Oncology and have the potential to make a significant impact upon the management of patients with brain tumors. Three highly integrated and synergistic projects are planned: Project 1: Improved management of GBM by integrated imaging and tissue analysis. Project 2: Image guided genome-epigenome analysis of tumor heterogeneity and evolution and Project 3: Hyperpolarized carbon 13 MRSI monitoring of pyruvate metabolism to assess drug action. The overall specific aims of the P01 are: 1) To accurately define tumor burden in the post treated setting. Projects 1 and 3 will assess the role of novel imaging techniques to assess tumor burden. 2) To characterize intratumoral heterogeneity (imaging parameters, histologic characteristics, genetic/epigenetic features) and the effect on treatment response, tumor evolution and clinical outcome. Projects 1 and 2 will be integrated to accomplish this aim. 3) To assess early response to therapy to assist with treatment decisions. Projects 1 and 3 will accomplish this aim through the clinical development and application of hyperpolarized C-13 imaging in conjunction with physiological and metabolic imaging techniques. Three shared resources (Administrative and Clinical Services Core, Biospecimen and Biostatistics Core and the Imaging Core) will provide key services that are essential for the Projects to accomplish their aims.
This P01 will address key challenges related to the accurate determination of tumor burden in the post treated setting, to the evaluation of tumor heterogeneity, which hampers the selection of appropriate therapies, and to the early assessment of response to therapy in patients with GBM. This is critical for optimizing clinical care and will have a significant impact on the development of new treatment strategies.
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|Radoul, Marina; Chaumeil, Myriam M; Eriksson, Pia et al. (2016) MR Studies of Glioblastoma Models Treated with Dual PI3K/mTOR Inhibitor and Temozolomide:Metabolic Changes Are Associated with Enhanced Survival. Mol Cancer Ther 15:1113-22|
|Bell, Robert J A; Rube, H Tomas; Xavier-MagalhÃ£es, Ana et al. (2016) Understanding TERT Promoter Mutations: A Common Path to Immortality. Mol Cancer Res 14:315-23|
|Nelson, Sarah J; Li, Yan; Lupo, Janine M et al. (2016) Serial analysis of 3D H-1 MRSI for patients with newly diagnosed GBM treated with combination therapy that includes bevacizumab. J Neurooncol 130:171-179|
|Cao, Peng; Zhang, Xiaoliang; Park, Ilwoo et al. (2015) (1) H-(13) C independently tuned radiofrequency surface coil applied for in vivo hyperpolarized MRI. Magn Reson Med :|
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