This proposal, by a multidisciplinary group of investigators with expertise in cancer proteomics and cancer prevention, is focused on the application of a proteomic approach for the development of cancer biomarkers. Novel technologies for protein analysis allow the detection and identification of proteins secreted by tumor cells as well as protein antigens that induce a humoral response as a result of their overexpression, increased turnover, post- translational modification or other unique processing in neoplastic cells. There is evidence that a humoral response to such protein antigens may predate the diagnosis of cancer, indicating the utility of assays for specific tumor protein antigens or antibodies, in addition to assays of increased levels of secreted proteins, for the early detection of cancer. Secreted proteins and tumor antigens or antibodies, because of their nature, may be detectable in serum and biological fluids. The initial targeted tumor types for the identification of potential biomarker proteins are: GI (colon, liver and esophagus), lung and ovary. However, as a Biomarkers Development Laboratory, we envisage applying the strategy based on the identification of secreted proteins and of tumor antigens to a variety of other tumors, as part of the Early Detection Research Network. The proposed research studies will make heavy utilization of two-dimensional protein analysis and of protein identification technologies that have been developed by the applicant group. Preliminary data derived from the analysis of different tumor types indicate the feasibility of this approach which has yielded a number of promising markers. A network for the procurement of serum and tissues from subjects with cancer or with preneoplastic lesions to achieve the goals of this project has been put into place by the applicant group. Participating institutions include CCOP affiliates of the University of Michigan CCOP Research base for cancer prevention. In addition, an agreement is in place with an industrial collaborator to assist in the further development of high-throughput and sensitive assays for protein and antibody detection in blood samples. The proposed studies will likely yield a large battery of novel secreted proteins and tumor antigens. Strategies are in place for potential markers, once identified, to determine their value in identifying cancer at an early stage or for risk assessment. This Biomarkers Development Laboratory is expected to substantially contribute to the goal of developing biomarkers for early detection.
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