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.
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.
|Figueroa, Javier; Phillips, Lynette M; Shahar, Tal et al. (2017) Exosomes from Glioma-Associated Mesenchymal Stem Cells Increase the Tumorigenicity of Glioma Stem-like Cells via Transfer of miR-1587. Cancer Res 77:5808-5819|
|Narang, Shivali; Kim, Donnie; Aithala, Sathvik et al. (2017) Tumor image-derived texture features are associated with CD3 T-cell infiltration status in glioblastoma. Oncotarget 8:101244-101254|
|Carstens, Julienne L; Correa de Sampaio, Pedro; Yang, Dalu et al. (2017) Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer. Nat Commun 8:15095|
|Hu, Jingzhe; Salzillo, Travis C; Sailasuta, Napapon et al. (2017) Interrogating IDH Mutation in Brain Tumor: Magnetic Resonance and Hyperpolarization. Top Magn Reson Imaging 26:27-32|
|Lehrer, Michael; Bhadra, Anindya; Ravikumar, Visweswaran et al. (2017) Multiple-response regression analysis links magnetic resonance imaging features to de-regulated protein expression and pathway activity in lower grade glioma. Oncoscience 4:57-66|
|Koul, Dimpy; Wang, Shuzhen; Wu, Shaofang et al. (2017) Preclinical therapeutic efficacy of a novel blood-brain barrier-penetrant dual PI3K/mTOR inhibitor with preferential response in PI3K/PTEN mutant glioma. Oncotarget 8:21741-21753|
|Qian, Xu; Li, Xinjian; Cai, Qingsong et al. (2017) Phosphoglycerate Kinase 1 Phosphorylates Beclin1 to Induce Autophagy. Mol Cell 65:917-931.e6|
|Van Roosbroeck, Katrien; Fanini, Francesca; Setoyama, Tetsuro et al. (2017) Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers. Clin Cancer Res 23:2891-2904|
|Gressot, Loyola V; Doucette, Tiffany; Yang, Yuhui et al. (2017) Analysis of the inhibitors of apoptosis identifies BIRC3 as a facilitator of malignant progression in glioma. Oncotarget 8:12695-12704|
|Jiang, Hong; Rivera-Molina, Yisel; Gomez-Manzano, Candelaria et al. (2017) Oncolytic Adenovirus and Tumor-Targeting Immune Modulatory Therapy Improve Autologous Cancer Vaccination. Cancer Res 77:3894-3907|
Showing the most recent 10 out of 208 publications