The goals of this proposal are to improve treatment for gliomas by enhancement of oncolytic therapy and to develop serum microvesicles as biomarkers for genetic and phenotypic properties of individual GBM tumors and their response to therapy. Project 1 (Chiocca/Kaur) will evaluate whether viral RNA in microvesicles produced by HSV-infected glioma cells increases susceptibility of tumors to oncolysis, and assess viral and cellular mRNAs in tumor-derived serum microvesicles as biomarkers of oncolytic therapy. Project 2 (Weissleder/Hahko) will apply nanotechnology-based diagnostic magnetic resonance (DMR) to characterize micro vesicle number and antigenic profiles in serum based on proteins critical to oncogenesis using serum from mice and patients bearing glioblastoma (GBM) and undergoing different treatment paradigms. Project 3 (Breakefield) will characterize and enrich tumor-derived microvesicles serum using antibody-capture microfluidic chambers and quantities levels and mutations in GBM-related RNAs using serum samples as in Project 2. These projects will be supported by: Core A (Hochberg) to provide oversight for programmatic organization and neuropathology;Core B (Carter) to maintain a biorepository of human GBM tumor and longitudinal serum samples from patients undergoing standard-of-care therapy or clinical Phase l/ll trials, to supply de-identified samples to Project 2 and 3, and to carry out biostatistical correlations with clinical parameters;and Core C (Charest) to provide genetically engineered GBM mice with mutations representing driver mutations in two subtypes of human GBMs to Project 1, and de-identified tumor/serum samples and biostatistical correlations with tumor volume and survival time to Projects 2 and 3. This program will develop and evaluate new accessible serum biomarkers to facilitate evaluation of therapeutic paradigms in mouse models and human patients both in terms of real time response to therapy and mechanisms of resistance to therapy.
Malignant gliomas represent the single most costly and morbid neoplasm per capita. There is a desperate need for accessible biomarkers in these and other forms of cancer to identify genetic/phenotypic characteristics of individual tumors in order to optimize therapies and to monitor responses to therapy.
|Bronisz, Agnieszka; Godlewski, Jakub; Chiocca, E Antonio (2016) Extracellular Vesicles and MicroRNAs: Their Role in Tumorigenicity and Therapy for Brain Tumors. Cell Mol Neurobiol 36:361-76|
|Mineo, Marco; Ricklefs, Franz; Rooj, Arun K et al. (2016) The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches. Cell Rep 15:2500-9|
|Ricklefs, Franz; Mineo, Marco; Rooj, Arun K et al. (2016) Extracellular Vesicles from High-Grade Glioma Exchange Diverse Pro-oncogenic Signals That Maintain Intratumoral Heterogeneity. Cancer Res 76:2876-81|
|Jeong, Sangmoo; Park, Jongmin; Pathania, Divya et al. (2016) Integrated Magneto-Electrochemical Sensor for Exosome Analysis. ACS Nano 10:1802-9|
|van der Vos, Kristan E; Abels, Erik R; Zhang, Xuan et al. (2016) Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain. Neuro Oncol 18:58-69|
|Choudhury, Sourav R; Hudry, Eloise; Maguire, Casey A et al. (2016) Viral vectors for therapy of neurologic diseases. Neuropharmacology :|
|Zappulli, Valentina; Friis, Kristina Pagh; Fitzpatrick, Zachary et al. (2016) Extracellular vesicles and intercellular communication within the nervous system. J Clin Invest 126:1198-207|
|Maas, Sybren L N; Breakefield, Xandra O; Weaver, Alissa M (2016) Extracellular Vesicles: Unique Intercellular Delivery Vehicles. Trends Cell Biol :|
|Pucci, Ferdinando; Garris, Christopher; Lai, Charles P et al. (2016) SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions. Science 352:242-6|
|Turetsky, Anna; Lee, Kyungheon; Song, Jun et al. (2015) On chip analysis of CNS lymphoma in cerebrospinal fluid. Theranostics 5:796-804|
Showing the most recent 10 out of 191 publications