2008-2009 Research Grants

California Pacific Medical Center

Evaluation Of Anti-Viral Therapies As Treatment For Glioblastoma:

Dr. Charles Cobbs at the California Pacific Medical Center is exploring the relationship between human cytomegalovirus (CMV) and glioblastoma. Preliminary results from several studies, including a Phase I clinical trial at Duke using an anti-CMV vaccine strategy which indicated a highly significant increase in time to progression for GBM patients compared to control, present a compelling argument for further investigation into the role of CMV infection in glioma pathogenesis. This study will seek to develop critical information toward understanding the role of CMV in glioma biology and whether anti-viral therapeutic strategies could be used to treat such cancers.

Is There a Brain Tumor Virus?

Children’s National Medical Center

Investigation of Novel Agents Directed Against Ras and Rac Proteins Shown to Critically Promote Tumor Growth, Migration and Metastasis:

Dr. Tobey MacDonald at Children’s National Medical Center is studying the association of the overexpression of the platelet-derived growth factor (PDGFR) pathway and its constituents, such as Ras and Rac, with metastatic medulloblastoma. Rac, in particular, has been shown to be critical for the promotion of tumor cell movement and metastasis. Because the Ras-Rac molecular axis target may be critical for tumor cell migration and cell movement, it is believed that agents addressing this target may be broadly effective in preventing invasive growth and metastasis in CNS and other tumors.

Duke University

Preclinical Screening Program

When ABC2 was launched in 2001, one of the most critical In 2002, Accelerate Brain Cancer Cure and the Preston Robert Tisch Brain Tumor Center at Duke University formed the Preclinical Screening Program, a groundbreaking collaboration that establishes a critical missing link between the biopharmaceutical industry’s efforts to produce potentially life-saving drugs and the theoretical knowledge at the cutting edge of scientific inquiry. Funding allows researchers from any sector - academia, industry, and government - to submit compounds that hold the potential to benefit brain cancer research to Duke for screening, free of charge.

This program encourages researchers, corporations, and federal agencies to test both approved and experimental therapies that target other types of cancers for their potential benefit to brain cancer patients. This program is run by an active Executive Committee managed by Accelerate Brain Cancer Cure.

How it Works
Accelerate Brain Cancer Cure and Duke consider requests from drug sponsors for preclinical evaluation. If there is agreement to test the potential therapies, a Material Transfer Agreement (MTA) is created. Once the MTA is signed, testing is initiated. Jointly, Accelerate Brain Cancer Cure and Duke are focused on accountability and maintain frequent interaction during all potential therapy testing.

Impact
To date, more than 150 compounds have been tested or are in under consideration for this program. The researchers at Duke have initiated trials for 18 therapies in brain tumor patients on the basis of results obtained through the Duke Preclinical Testing Program.

Institute for Systems Biology

Development of a GDxBase Informatics Resource to Collect and Analyze GBM-related Research Data

Drs. Nat Goodman and Leroy Hood at Seattle’s Institute for Systems Biology will work with ABC2 to develop a GDxBase informatics system, web portal and accompanying software tools based on a framework for disease-oriented websites developed by ISB and its collaborators. This resource will enable the creation of a comprehensive database and analytical framework to assess relationships between the various ongoing and historical brain cancer research initiatives. Following a review of published research studies, ISB will identify gaps in research and test for correlations between unconnected research projects.

University of California, San Francisco

Investigation of Mechanisms of Oncogene Addiction Towards EGFR and Active Site Titration of EGFR Using Chemical Genetics

Working jointly with the Samuel Waxman Cancer Research Foundation, ABC² is supporting the efforts of Drs. William Weiss and Kevan Shokat at UCSF to generate EGFR mutants, high-throughput screening capabilities, chemical genetic technologies, transcriptional techniques, and small molecule inhibitors to enable the investigators to quantify the ability of kinase inhibitors to block their primary targets; to develop new assays to identify patients who might benefit from targeted kinase inhibitor therapies, and to perform preclinical testing of novel EGFR-inhibitor based therapies with improved efficacy.

University of California, Los Angeles

Exploration of Novel Mechanisms by Which EGFR/PI3K Signaling Promotes Glioblastoma Survival Through the Master Lipid Regulator SREBP1

The EGFR/PI3K pathway is activated in nearly 50% of glioblastoma patients, but clinical responses to EGFR kinase inhibitors have been infrequent and short-lived. In this study Drs. Paul Mischel and Tim Cloughesy will explore mechanisms by which EGFR/PI3K signaling promotes glioblastoma survival through the master lipid regulator SREBP1 and will test whether FAS inhibitors alone or in combination with the lipophilic HMG-CoA Reductase inhibitor lovastatin will kill EGFR-activated glioblastomas in intracranial xenografts.