The objectives of the UCLA SPORE in Brain Cancer are to contribute significantly to progress in the diagnosis, prognosis, and treatment of brain cancer. These goals will be accomplished through multiple and diverse research projects involving mechanistic pre-clinical work and innovative clinical studies, with a particular focus on developing novel strategies to overcome the problem of treatment resistance. The broad, long-term objectives and aims of our brain cancer SPORE are as follows: 1) to investigate mechanisms of immune evasion following active immunotherapy, and develop rational combinations of immunotherapeutic strategies to overcome the immunosuppressive milieu of the brain tumor microenvironment; 2) to elucidate the alterations in metabolism associated with targeted therapy resistance, and exploit these metabolic vulnerabilities to induce intrinsic apoptosis of tumor cells; 3) to explore the concept of radiation-induced phenotype conversion of non-tumorigenic cells to glioblastoma-initiating cells as a mechanism for radiation resistance, and test new therapeutics to block such glioma stem cell conversion; and 4) to investigate the pathways of resistance to IDH inhibitors, and utilize novel epigenetic pathways to sensitize IDH-mutant gliomas to treatment. In order to achieve these translational research goals of our program, we propose four main projects involving: 1) active immunotherapy combined with immune checkpoint modulation for glioblastoma; 2) targeting metabolic vulnerabilities in glioblastoma cells; 3) inhibition of radiation-induced phenotype conversion to glioma-initiating stem cells; and 4) novel epigenetic treatment of IDH mutant gliomas. These translational research projects will be supported by shared resource cores in administration, biospecimen/pathology, neuroimaging, and biostatistics/bioinformatics/data management. Our program will also be responsive to SPORE themes by incorporating Developmental Research and Career Enhancement Programs in order to foster new approaches for assessing and treating brain cancer. Our diverse array of novel projects and state-of-the-art cores will likely make a significant impact on brain cancer patient care. Each project has been developed jointly by teams of basic and clinical researchers working together in a trans-disciplinary manner to address the most vexing problem in brain cancer ? the development of treatment resistance. All four projects are highly translational and will reach human endpoints within the context of this SPORE grant period.

Public Health Relevance

Overall: UCLA SPORE in Brain Cancer NARRATIVE The UCLA Brain Cancer SPORE will support research into new and innovative strategies to diagnose and treat brain cancer, particularly focusing on novel ways to overcome the problem of treatment resistance. Despite many different treatment approaches, the five-year survival rate for glioblastoma (WHO grade IV glioma) patients is still <5%, and there are no definitive cures for this disease. Thus, the proposed research is of relevance to public health, as there is clearly an unmet need for patients with this type of cancer and novel therapeutic approaches are warranted.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
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Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Arnold, Julia T
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Pope, Whitney B (2018) Brain metastases: neuroimaging. Handb Clin Neurol 149:89-112
Li, Tie; Cox, Christopher D; Ozer, Byram H et al. (2018) D-2-Hydroxyglutarate Is Necessary and Sufficient for Isocitrate Dehydrogenase 1 Mutant-Induced MIR148A Promoter Methylation. Mol Cancer Res 16:947-960
Magaki, Shino; Parks, Robyn; Vinters, Harry V et al. (2018) A 44-Year-Old Female with Familial Mediterranean Fever, Cardiomyopathy and End Stage Renal Disease. Brain Pathol 28:135-136
Kepe, Vladimir; Scafoglio, Claudio; Liu, Jie et al. (2018) Positron emission tomography of sodium glucose cotransport activity in high grade astrocytomas. J Neurooncol 138:557-569
Calais, Jeremie; Czernin, Johannes; Cao, Minsong et al. (2018) 68Ga-PSMA-11 PET/CT Mapping of Prostate Cancer Biochemical Recurrence After Radical Prostatectomy in 270 Patients with a PSA Level of Less Than 1.0 ng/mL: Impact on Salvage Radiotherapy Planning. J Nucl Med 59:230-237
Gallaher, Sean D; Fitz-Gibbon, Sorel T; Strenkert, Daniela et al. (2018) High-throughput sequencing of the chloroplast and mitochondrion of Chlamydomonas reinhardtii to generate improved de novo assemblies, analyze expression patterns and transcript speciation, and evaluate diversity among laboratory strains and wild isolates. Plant J 93:545-565
Ellingson, Benjamin M; Wen, Patrick Y; Cloughesy, Timothy F (2018) Evidence and context of use for contrast enhancement as a surrogate of disease burden and treatment response in malignant glioma. Neuro Oncol 20:457-471
Liau, Linda M; Ashkan, Keyoumars; Tran, David D et al. (2018) First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med 16:142
Majedi, Fatemeh S; Hasani-Sadrabadi, Mohammad Mahdi; Kidani, Yoko et al. (2018) Cytokine Secreting Microparticles Engineer the Fate and the Effector Functions of T-Cells. Adv Mater 30:
Ellingson, Benjamin M; Abrey, Lauren E; Nelson, Sarah J et al. (2018) Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma. Neuro Oncol 20:1240-1250

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