The Animal Core will provide SPORE investigators robust animal models that recapitulate key molecular and histologic phenotypes of human GBM tumors through the development and maintenance of a panel of serially transplantable GBM tumor lines and brain tumor initiating cell (BTIC) that are carefully characterized for key molecular and functional features. These tumor models are more clinically relevant than established cell lines grown as xenografts. This observation has many implications for neuro-oncology research, but is likely to be of greatest importance for testing experimental therapeutics. We believe that testing novel therapeutics regimens in these xenograft and BTIC models will provide more accurate translation of results into clinical efficacy in human trials. During the previous funding cycle, resources provided by this Core were used in 41 peer reviewed publications and were integral components in 8 extramurally funded grant applications. During the current funding period, the Animal Core will continue with 8 key functions: 1. Initiate passage, and archive xenograft tumors and brain tumor initiating cultures (BTIC) from GBM patients 2. Compare tumors derived from BTIC vs. direct xenografting of patient tissue. 3. Provide detailed molecular and functional characterization of each xenograft line. 4. Collect, process, and distribute xenograft and BTIC tumor samples within and beyond the SPORE. 5. Coordinate and conduct in vivo experiments using the xenograft/BTIC panel. 6. Coordinate and conduct imaging studies using the xenograft/BTIC panel. 7. Establish secondary models for therapeutic resistance in select xenograft lines. 8. Maintain up-to-date records on all BTIC cultures, xenograft tissues and related biospecimens. All specimens will be collected and processed under tight quality control, and will be distributed to SPORE researchers or banked for future SPORE research projects. The SPORE Pathology and Tissue Procurement Core will assure that specimens are property fixed, stained, and histologically evaluated. The Clinical Research Core will ensure that patients are property consented for use of their tumor tissues in establishing xenograft tissues and BTICs, will provide clinical outcome for the patients, and will ensure normal tissue samples are collected and archived for potential future studies. Finally, the Biostatistics Core will support statistical analyses and interpretation of the studies performed within the Core.
The development and use of clinically relevant tumor models is essential for successful translation of novel therapeutic strategies into clinical practice. The Animal Core will develop, characterize and use highly relevant xenograft and brain tumor initiating cultures for testing therapeutic strategies within this application.
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