This MD Anderson Brain Cancer SPORE renewal application builds upon the significant progress achieved in the initial funding period, including the development of novel biological (oncolytic virus, stem cells), targeted (PI3K inhibitors), and immunomodulaton (p-STAT-3 inhibition) therapeutic strategies;as well as the development of biomarkers that inform personalized care of GBM patients. In this renewal, our goal is to capitalize on these prior successes in order to dramatically improve the survival of patients with malignant gliomas. We have established a multidisciplinary, integrated, flexible, and highly translational (bench to bedside and back) research program that aims to discover and rationally test new biologic, targeted, and immunological therapies, and that seeks to develop prognostic and predictive biomarkers that inform individualized approaches to GBM treatment. To achieve our goals we propose four fully translational research projects (3 therapeutic;1 population-based), all of which incorporate tissue-based clinical trials, and are supported by five Cores: Administrative (A), Pathology and Biorepository (B), Biostatics and Bioinformatics (C), Clinical (D), and Animal (E). The Developmental Research Program (DRP) and Career Development Program (CDP) continue as successful aspects of our SPORE as they encourage novel studies and promote young investigators.
The aims of the four projects are to: Project 1: Enhance the efficacy of a novel oncolytic adenovirus, Delta-24-RGD, by combining it with temozolomide, by exploiting autophagy, and by improving delivery using bone marrow stem cells; Project 2: Explore combinatorial targeted strategies based on PISKinase inhibition by elucidating mechanisms of single-drug escape in a large collection of patient-derived glioma stem cells and tumor specimens; Project 3: Validate in phase III trials a new robust GBM prognostic classifier, the molecular-clinical prognosticator (MCP), and develop clinical diagnostics that predict response to bevacizumab an ipilimumab; Project 4: Modulate GBM induced immunosuppression using a novel p-STAT-3 inhibitor, WP1066. Through this research program and with the full support of The University of Texas M.D. Anderson Cancer Center, this SPORE will make a significant impact toward the diagnosis and treatment of patients with malignant brain tumors.

Public Health Relevance

Over the past 20 years, advances in the treatment of glioblastoma, the most common malignant brain tumor, have been only incremental. If successful, the research proposed in this Brain Cancer SPORE grant will legitimize novel, mechanistically unique therapeutic approaches and validate prognostic and predictive biomarkers, and thereby change the standards of care of patients with brain tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA127001-06
Application #
8548737
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (M1))
Program Officer
Arnold, Julia T
Project Start
2007-04-01
Project End
2018-08-31
Budget Start
2013-09-17
Budget End
2014-08-31
Support Year
6
Fiscal Year
2013
Total Cost
$2,042,322
Indirect Cost
$765,871
Name
University of Texas MD Anderson Cancer Center
Department
Neurosurgery
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Lu, Sean; Wang, Yugang (2018) Nonmetabolic functions of metabolic enzymes in cancer development. Cancer Commun (Lond) 38:63
Qiao, Yang; Gumin, Joy; MacLellan, Christopher J et al. (2018) Magnetic resonance and photoacoustic imaging of brain tumor mediated by mesenchymal stem cell labeled with multifunctional nanoparticle introduced via carotid artery injection. Nanotechnology 29:165101
Zinn, Pascal O; Singh, Sanjay K; Kotrotsou, Aikaterini et al. (2018) A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models. Clin Cancer Res 24:6288-6299
Shah, Maitri Y; Ferracin, Manuela; Pileczki, Valentina et al. (2018) Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations. Genome Res 28:432-447
Mostovenko, Ekaterina; Végvári, Ákos; Rezeli, Melinda et al. (2018) Large Scale Identification of Variant Proteins in Glioma Stem Cells. ACS Chem Neurosci 9:73-79
Chen, Zhihua; Morales, John E; Guerrero, Paola A et al. (2018) PTPN12/PTP-PEST Regulates Phosphorylation-Dependent Ubiquitination and Stability of Focal Adhesion Substrates in Invasive Glioblastoma Cells. Cancer Res 78:3809-3822
Wang, Yugang; Xia, Yan; Lu, Zhimin (2018) Metabolic features of cancer cells. Cancer Commun (Lond) 38:65
Noh, Hyangsoon; Zhao, Qingnan; Yan, Jun et al. (2018) Cell surface vimentin-targeted monoclonal antibody 86C increases sensitivity to temozolomide in glioma stem cells. Cancer Lett 433:176-185
Lee, Jong-Ho; Liu, Rui; Li, Jing et al. (2018) EGFR-Phosphorylated Platelet Isoform of Phosphofructokinase 1 Promotes PI3K Activation. Mol Cell 70:197-210.e7
Lang, Frederick F; Conrad, Charles; Gomez-Manzano, Candelaria et al. (2018) Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma. J Clin Oncol 36:1419-1427

Showing the most recent 10 out of 232 publications