Funded Grants

Project Sponsor: David Geffen School of Medicine at UCLA

Project Title: Active vaccination and the timing of checkpoint blockade dictate effective immunotherapy for glioblastoma

Project Manager: Robert Prins

Project Sponsor: McGill University

Project Title: Harnessing the brain tumor immune-microenvironment to enhance therapeutic efficacy

Project Manager: Daniela Quail

Project Sponsor: UPMC Children’s Hospital of Pittsburgh

Project Title: Interrogating anti-tumor T-cells To develop adoptive cell transfer (ACT) Immunotherapy for pediatric high-grade gliomas

Project Manager: Gary Kohanbash

Sponsoring Institution: University of California, San Francisco

Project Title: Three dimensional immuno-genomics approach to personalized neoantigen-based immunotherapy

Project Manager: Joseph Costello

Dana-Farber Cancer Institute in support of European Organisation for Research and Treatment of Cancer (EORTC)

Project Managers: Michael Weller, M.D. and Co-PM: Patrick Yung Wen, M.D.

“Molecular genetic host-derived and clinical determinants of long-term survival in glioblastoma”

Year: 2014

Amount: $2,000,000 over 2 years

Children’s Hospital Boston

Investigator: Edward R. Smith

Urinary Biomarkers for Non-invasive Assessment of Therapeutic Efficacy in Glioma

Emory University School of Medicine

Investigator: Erwin G. Van Meir

Development of Protein Arrays for the Detection of Biomarkers in the CSF of Brain Tumor Patients

Johns Hopkins University

Investigator: Jaishri O. Blakeley

Amide Proton Transfer MR Imaging to Assess Tumor Response in Patients with Gliomas

Johns Hopkins University

Investigator: Luis A. Diaz

Circulating Tumor DNA as a Dynamic Biomarker in Malignant Gliomas

Johns Hopkins University

Investigator: Alena Hoská

Non-invasive Assessment of Glutamate in Glioblastoma Multiforme: Effect of Treatment

Massachusetts General Hospital

Investigator: Bob S. Carter

Exosome Analysis: A Non-Invasive Approach to Monitor Treatment Responses in Glioma Patients

Memorial Sloan-Kettering Cancer Center

Investigator: Andrew B. Lassman

Molecular Determinants of [18F]FACBC-PET Imaging in Brain Tumors

University of California (David Geffen School of Medicine at UCLA)

Investigator: Whitney B. Pope

Combining Genomics with Physiologic Imaging Biomarkers to Predict and Follow Treatment Response in Glioma

University of Texas MD Anderson Cancer Center

Investigator: Kenneth D. Aldape

A combined molecular and clinical predictor of progression vs. pseudoprogression in newly diagnosed GBM.

University of Washington

Investigator: Kristin R. Swanson

Patient-specific Metrics of Treatment Response

Vanderbilt University Medical Center

Investigator: Kyle D. Weaver

Monitoring Response to Therapy in Malignant Glioma Patients Using Blood-Based Epigenomic and Proteomic Biomarkers

Kennedy- Krieger Institut

Dr. John J. Laterra

Tumor Stem Cell-Based Drug Discovery for Adult and Pediatric Glioma

Pre-clinical models of malignant brain tumors remain important in the identification of anti-cancer compounds. Unfortunately, the cell culture and animal models currently used for drug discovery have deficiencies that limit their ability to predict therapeutic responses in patients. A potentially critical explanation for this deficiency is that past models inadequately address possibility that a small subpopulation of glioma cancer cells with stem cell-like properties (i.e. glioma cancer stem cells) may generate the bulk of cancer cells within each tumor. This emerging concept predicts that therapies will fail if they do not specifically target the cancer stem cells and stem cell-driven tumor recurrence. The hypothesis of this 3-year research program is that stem cell-like cancer cells in glioma are a necessary and specific primary target for therapeutic intervention. We propose to pursue this hypothesis, looking at both adult and pediatric gliomas, with a new collaborative network of scientists and clinicians from four academic institutions within the United States and Italy who are experts in the fields of basic stem cell biology, cancer biology, molecular genetics, neuropathology, neuro-oncology, neurosurgery, neuroradiology, experimental therapeutics, and clinical trial design.

David Geffen School of Medicine at UCLA

Investigator: Dr. Paul Mischel

Molecularly Guided Clinical Trials for Glioma

Malignant glioma is a disease with great genetic complexity. The traditional research approach of analyzing individual genes or proteins in isolation has yielded few breakthroughs; a paradigm shift is needed. Diverse types of high dimensional molecular (and clinical) data must be integrated to identify effective combinations of therapeutic agents and novel drug targets. We hypothesize that a systems level integration will facilitate the development and testing of new glioma treatments. The recent finding of the critical role for molecular interactions in determining response to EGFR kinase inhibitors highlights this point. Efficient translation using dynamic models and the design of prospective “smart” clinical trials will require a new type of team. The assembled team, with complementary expertise, diverse perspectives, a range of clinical populations (both adult and pediatric gliomas) and a history of successful collaboration should facilitate the development of innovative new treatments for malignant glioma patients. The focus will be on using an integrated systems approach to accelerate discovery, biologic modeling, and clinical application of novel molecular therapeutic targets in malignant glioma.

Radiation Therapy Oncology Group

Investigator: Dr. Minesh Mehta

Identifying and Overcoming Resistance Mechanisms in Glioblastomas: A Joint EORTC-RTOG Effort

Currently available treatments for glioblastoma can prolong survival in some patients, but are rarely curative. Fundamentally new approaches are required to uncover biological mechanisms of resistance from which novel therapeutic strategies can be developed. As glioblastomas are relatively uncommon tumors, there is only a limited ability of single institutions to conduct studies with adequate power to address these issues. Accordingly, the Radiation Therapy Oncology Group (RTOG) and European Organization for Research and Treatment of Cancer (EORTC) have joined forces in initiating the largest clinical study to date for newly-diagnosed glioblastomas. The required submission of tissue specimens within this carefully managed clinical trial system will create unparalleled translational research resources with enormous potential to uncover mechanisms of therapeutic resistance in glioblastomas. The BTFC is supporting the research component, a valuable leveraging of the unprecedented clinical trial infrastructure. The working hypothesis of the team is that designing more effective therapeutic strategies for glioblastoma patients will be optimized via a pharmacogenomic/pharmacoproteomic approach. Mechanisms of resistance identified through molecular and genetic profiling of large numbers of prospectively-collected clinical specimens will be hopefully lead to the development of targeted therapy strategies to overcome observed mechanisms of glioma resistance.