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Core A – Pathology

Keith Ligon, MD, PhD (DFCI)
David Louis, MD (MGH)

The overall goal of this SPORE application is to develop more effective targeted molecular therapies and biomarkers for glioblastoma. The four proposed projects focus on 1) Overcoming resistance to VEGF inhibition by targeting Angiopoietin-2; 2) Inhibiting the phosphatidylinositol 3-kinase (PI3 kinase) pathway; 3) designing novel strategies for imaging and targeting IDH mutant gliomas; and 4) Increasing the radiosensitivity of glioblastomas by inhibiting the bHLH transcription factor Olig2. One of the innovative themes of this SPORE proposal is that biospecimens collected by the Pathology Core will be comprehensively molecularly profiled using multiplexed technologies so projects may effectively evaluate the interaction of targeted therapies and their targets.

The Pathology Core will support the goals of the SPORE by providing expert neuropathological review, biospecimen banking and clinical trial support. In addition, the Pathology Core will be a centralized resource for clinically and molecularly annotated glioblastoma tissues and primary glioblastoma cell cultures that will be essential to the success of the proposed projects. By centralizing these activities, the Pathology Core will ensure the safe and effective use of finite glioblastoma tissue resources without limiting the scope of the translational research planned in this proposal. The SPORE support, combined with significant institutional support for these goals, will ensure that over the next 5 years the Pathology Core will provide the critical research infrastructure required for successful, collaborative translational research of the SPORE program.

Core B – Biostatistics

Dianne Finkelstein, PhD

The Biostatistics Core provides statistical support for the research conducted in the brain cancer SPORE program, including related database and computing requirements. The Core provides consultation and expertise on the development and implementation of plans for data collection, particularly the coding convention and variable format required for statistical analysis. The Core contributes to the data management plan, including form design and database requirements, during development of the SPORE related clinical trials. The Core provides expertise and resources for data transfer, merging, sharing and security while maintaining the confidentiality of all patient-related protected health information. The Core provides ready and dedicated access to statistical expertise for the design, planning and conduct of preclinical experiments, clinical trials and correlative tissue and biomarker studies. Analysis of the clinical trials will include interim monitoring, if necessary, including the stopping rules for safety and futility. The Core also provides statistical expertise for data analysis and interpretation of research studies, including manuscript preparation.

Core C – Administration

Tracy Batchelor, MD (MGH)
Charles Stiles, PhD (DFCI)

This SPORE grant is intended to support multi-project, interdisciplinary and multi-institutional translational research in glioblastoma. The governance structure of this DF/HCC SPORE grant provides the foundation for the implementation, execution and ultimate success of all projects and cores. The Administration Core serves as the “hub” for this governance structure and aims to achieve a number of specific objectives as defined below. The SPORE Director and Co-Director are senior administrators and researchers who have worked together on prior DF/HCC initiatives and who provide strong, complementary leadership for the grant. The trans-institutional administrative team consists of senior personnel at DF/HCC institutions who have worked together effectively on multiple brain cancer projects. There are two senior clinical and imaging scientists into the Administration Core to supervise brain cancer SPORE-specific clinical trials and imaging studies, respectively, and to enable this SPORE to capitalize on existing DF/HCC Cores to support these types of studies. There is an effective internal and external committee structure to provide expertise, advice and oversight of the program. Each of the committees consists of collaborative, complementary members who have already worked together on prior collaborative projects. A series of regular SPORE meetings involving both administrative and scientific SPORE serve to facilitate close collaboration, troubleshooting and monitoring of the SPORE program. There is an effective internal and external communications program, which includes a brain cancer SPORE-specific component. An established and extensive DF/HCC communications infrastructure is utilized to promote open, regular, trans-institutional communication regarding SPORE opportunities and activities. There is an active SPORE program to enhance participation by underrepresented minorities and women.