This Preventive Interventions leadership application draws from two submitted U01 research applications. One application (C. Kemp and S. Hanash co-PIs) proposes to investigate mouse models of breast and lung cancer to Identify circulating protein markers applicable to breast and lung cancer in humans. The second (M. Disis, PI and S. Hanash, co-investigator) proposes to investigate mouse models of breast cancer to identify tumor antigens that induce an immune response in the form of autoantibodies that can be used for early diagnosis of breast cancer and that have potential for vaccine development. The team for the leadership application is augmented with investigators and resources in nutritional interventions and energy balance, chemoprevention, genomic and proteomic studies. Informatics resources and expertise include modeling, software and database development with the NCI's cancer bioinformatics grid (CaBIG) compatibility and integrative analysis of multi-dimensional data. The research program envisions a dual strategy, one consisting of studies in mouse models to better understand findings in humans stemming from genome-wide association studies (GWAS) and other genomic studies;findings from chemoprevention studies that benefit from further investigations using mouse models and findings from environmental exposures, diet and calorie expenditure studies. The second strategy consists of studies in mouse models that will lead to subsequent studies in humans and includes identification of candidate biomarkers using mouse models that would be applicable for early detection and for assessment of tumor recurrence;testing of chemoprevention agents in mouse models;and identification of tumor antigens in mouse models that are potentially applicable to humans for early detection and.of targets for vaccine development. The leadership team will also contribute to advancing the mission of MMHHC by facilitating interactions and joint activities within the Prevention Cluster and between clusters and other NCI programs and the broader scientific community and by sharing resources to be developed through the leadership program.

Public Health Relevance

There is a crucial need for innovative strategies for cancer prevention. We have assembled a multi-disciplinary team to take full advantage of the availability of mouse models of cancer to coordinate effort aimed at first testing strategies for cancer prevention in mouse models to make informed choices for cancer prevention in humans through nutritional intervention, through blood based screening and diagnosis and through boosting of the immune system to fight cancer at its earliest stages.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZCA1-SRLB-Q (M1))
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Marks, Cheryl L
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Fred Hutchinson Cancer Research Center
United States
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Busch, S E; Moser, R D; Gurley, K E et al. (2014) ARF inhibits the growth and malignant progression of non-small-cell lung carcinoma. Oncogene 33:2665-73
Kemp, Christopher J; Moore, James M; Moser, Russell et al. (2014) CTCF haploinsufficiency destabilizes DNA methylation and predisposes to cancer. Cell Rep 7:1020-9
Ruddell, Alanna; Croft, Alexandra; Kelly-Spratt, Karen et al. (2014) Tumors induce coordinate growth of artery, vein, and lymphatic vessel triads. BMC Cancer 14:354
Moser, Russell; Xu, Chang; Kao, Michael et al. (2014) Functional kinomics identifies candidate therapeutic targets in head and neck cancer. Clin Cancer Res 20:4274-88
Mao, Jianning; Ladd, Jon; Gad, Ekram et al. (2014) Mining the pre-diagnostic antibody repertoire of TgMMTV-neu mice to identify autoantibodies useful for the early detection of human breast cancer. J Transl Med 12:121
Busch, Stephanie E; Gurley, Kay E; Moser, Russell D et al. (2012) ARF suppresses hepatic vascular neoplasia in a carcinogen-exposed murine model. J Pathol 227:298-305