Summary Overall Core. The Center for Pre-Clinical Cancer Research (Cancer COBRE) aims to identify clinically relevant mechanisms of human cancer disease using models that closely reflect the disease state in the context of the tumor microenvironment. Recent advances in 3D tumor culture techniques have intensified the focus on in vitro human cell culture systems to reveal insights into human tumorigenesis and thus drive novel therapeutic discovery. Promising Junior Investigators (PJIs) address devastating human cancer diseases that exhibit poor outcomes in patients and for which there are unmet therapeutic needs. The four PJI projects feature osteosarcoma, breast cancer, liver cancer, and prostate cancer as diseases that would benefit from pre-clinical models that are more predictive of mechanistic efficacy in humans. All of the PJI projects will use specialized in vivo mouse models and/or in vitro 3D tumor spheroids to identify relevant mechanisms of tumorigenesis or for evaluation of novel therapeutic strategies. The Center will promote a unified and coordinated approach by establishing a new specialized core facility, Pre- Clinical Evaluation Core (PCEC), to provide scientific expertise and technical support for the pre-clinical evaluation of the PJI projects. The unique PCEC will provide a centralized approach that will support exploratory and translational assessment of cancer disease mechanisms and therapeutic strategies in humans. To accomplish this approach, advanced 3D cell culture systems will provide critical translational information. and bridge the gap between animal models and human therapeutic outcomes. The new Molecular Biology and Immunopatholgy Core (MBIPC) will provide access to state-of-the-art equipment and expertise in Molecular Biology and Immunopathology while leveraging extensive resources at LSU SVM. Human and animal diseases are a major focus at the LSU SVM and on the LSU campus. The Center has three Aims: Aim 1. To create a Center for Pre-Clinical Cancer Research to promote and support centralized management and coordination of pre-clinical evaluation of tumorigenesis mechanisms and translational therapeutic approaches. Aim 2. To provide the COBRE PJIs and other investigators with a core infrastructure for resources and support for advanced pre-clinical cancer disease research that will enhance PJI individual competitiveness for extramural funding. Aim 3. To provide training and mentorship on pre-clinical evaluation using state-of-the-art in vitro 3D tumor spheroids to complement in vivo cance disease modeling.

Project narrative Overall The Center for Pre-Clinical Cancer Research (Cancer COBRE) aims to identify clinically relevant mechanisms of human cancer disease using models that closely reflect the disease state in the context of the tumor microenvironment. The four PJI projects feature osteosarcoma, breast cancer, liver cancer, and prostate cancer as diseases that would benefit from pre-clinical models that are more predictive of mechanistic efficacy in humans. All of the PJI projects will use specialized in vivo cancer mouse models and/or in vitro 3D spheroids to identify relevant mechanisms of tumorigenesis or for evaluation of novel therapeutic strategies. The Center will promote a unified and coordinated approach by establishing new specialized core facilities 1) Pre-Clinical Evaluation Core (PCEC) to provide scientific expertise and technical support for the pre-clinical evaluation and Molecular Biology and Immunopatholgy Core (MBIPC) to provide access to state-of-the-art equipment and expertise in Molecular Biology and Immunopathology for the PJI projects.