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.
|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|
|Wang, Qianghu; Hu, Baoli; Hu, Xin et al. (2018) Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment. Cancer Cell 33:152|
|Dong, Jianwen; Park, Soon Young; Nguyen, Nghi et al. (2018) The polo-like kinase 1 inhibitor volasertib synergistically increases radiation efficacy in glioma stem cells. Oncotarget 9:10497-10509|
|Thomas, Jonathan G; Parker Kerrigan, Brittany C; Hossain, Anwar et al. (2018) Ionizing radiation augments glioma tropism of mesenchymal stem cells. J Neurosurg 128:287-295|
|Lu, Zhimin; Hunter, Tony (2018) Metabolic Kinases Moonlighting as Protein Kinases. Trends Biochem Sci 43:301-310|
|Jacobs, Daniel I; Liu, Yanhong; Gabrusiewicz, Konrad et al. (2018) Germline polymorphisms in myeloid-associated genes are not associated with survival in glioma patients. J Neurooncol 136:33-39|
|Lu, Sean; Wang, Yugang (2018) Nonmetabolic functions of metabolic enzymes in cancer development. Cancer Commun (Lond) 38:63|
Showing the most recent 10 out of 232 publications