Brain SPORE Projects
In addition to meeting the fundamental requirements of the National Cancer Institute for translational research projects, the Brain SPORE projects are carefully designed to reflect the most innovative ways to generate advances in our understanding of glioma biology and reflect Mayo’s strengths in basic, translational, clinical and clinical trials research in gliomas. The investigative teams are interdisciplinary, and include both brain cancer researchers and clinicians who are experienced in patient oriented cancer research. In all cases, the projects are designed so that there is a clear translational trajectory within five years.
Project #1: Optimizing EGFR inhibitor-based therapies in glioblastoma
Dr. Sarkaria, working with other researchers including Caterina Giannini, M.D.; Wilma Lingle, Ph.D.; Charles Erlichman, M.D.; Joon Uhm, M.D.; Richard Vile, Ph.D.; Karla Ballman, Ph.D.; and Ann Tuma; seeks to understand the mechanisms by which tumor cells are killed using radiation and drugs that inhibit a protein which drives tumor growth and aggressiveness in glioma.
The overriding hypothesis of Project #1 is that novel approaches with epidermal growth factor receptor (EGFR) inhibitor-based small molecules can be identified by the use of a unique xenograft model of glioblastoma. In addition, the Project will learn if patients can be stratified for treatment based on an in vitro evaluation of molecular inhibitors of the EGFR pathway. This Project will involve the Biostatistics Core, the Pathology Core, the Xenograft Core, and the Clinical Research Core. It will interact with Project #3 in that the latter project will utilize the animal model and its response to the experimental therapeutics to assess the value of the proposed soluble EGFR as a biomarker.
Project #2: Targeted MV-CEA as a novel antitumor agent against gliomas
The Primary Investigators, working with colleagues Roberto Cattaneo, M.D., C. David James, Ph.D.; Jan Buckner, M.D.; Gregory Poland, M.D.; Michael Blanco, D.V.M.; Mark Federspiel, Ph.D.; Cory Petell; and Caterina Giannini, M.D.; are studying the effectiveness of delivering a modified measles virus directly into brain cancer tumors to kill cancer cells without harming normal cells.
The overriding hypothesis of Project #2 is that a replicating attenuated vaccine strain of measles virus (MV) will have potent antitumor activity against human glioma with an excellent safety profile. The project will involve in vitro and preclinical analyses of the efficacy and safety of MV-CEA, and it incorporates close interactions with the Biostatistics, Pathology, and Xenograft Cores.
Despite the many therapies that have been used to treat the most common type of brain tumors, known as glioblastoma multiforme (GBM), the prognosis for patients diagnosed with this aggressive tumor unfortunately remains poor. Because these tumors invade the surrounding brain, it is virtually impossible to remove an entire tumor by surgery. In addition, tumor cells that invade the surrounding normal brain tissue are highly resistant to radiation and chemotherapy.
These challenges underscore the need to better understand how brain tumor cells invade and, in so doing, to develop more effective treatments. The Primary Investigators are working together with a number of colleagues, including L. Gerard Toussaint III, M.D., Michael Berens, Ph.D., Jean Kloss and Zhongbo Yang to study Pyk2, a protein that brain cancers use to invade surrounding tissues, in an attempt to design treatments that inhibit invasion.
Project #4: Association of chromosome 19 q-arm polymorphisms with glioma development, survival and response to therapy
The overriding hypothesis of Project #4 is that there is a gene (or genes) on 19q13.3 that increases the risk of glioma and predicts survival and response to therapy. Project #4 will involve a prospective accumulation of blood samples in patients with glioma and appropriate controls and will involve extensive statistical analysis. This Project will be highly dependent on the Biostatistics, and Clinical Research Cores.
Drs. Yang and Jenkins will collaborate with Julie Cunningham, Ph.D.; Karla Ballman, Ph.D.; Terry Therneau, Ph.D.; Daniel Schaid, Ph.D.; and Mark Liebow, M.D.; to explore the genetic basis of brain tumors in order to help predict a specific tumor's response to treatment.
In addition to these research projects, the SPORE grant provides funding for a developmental research program to explore innovative research ideas and a career development program for the next generation of brain cancer scientists.
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