EARLY DETECTION OF CANCER BY AFFINITY MASS SPECTROMETRY

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Prostate and breast cancer are the most common cancers in men and women in the United States. Current diagnostic tests are not sensitive or specific enough to detect cancers in their early stages when the number of tumor cells is small and the chance for cure or control is greatest. Furthermore, no single biomarker is likely to improve early detection of these cancers. What are needed are better tools to determine the traits of the tumor, a profile that dictates early detection, treatment choice, and efficacy of treatment and predicts prognosis. The objective of this study is to identify the unique protein fingerprints that signal the presence of cancer with the long term goal of developing clinical assays to improve the early detection of prostate and breast cancers. The novel proteomic technology, designated Surface Enhanced Laser Ionization/Desorption (SELDI) ProteinChip mass spectrometry, will be used to meet this goal. The first Aim is devoted to discovery of the pre-cancerous and cancerous signature proteins in microdissected cancer cells. Pure population of cells from all developmental stages, i.e. normal, pre-neoplastic, hyperplatic, primary and metastatic lesions, will be SELDI analyzed to identify the unique cancer protein fingerprints. The second aim will identify which of these unique cancer-associated proteins are secreted/shed in body fluids. By comparing protein profiles of individual samples with composite reference maps of the cancer protein profiles, the potential clinical use of SELDI protein profiling as a diagnostic/prognostic test will be determined in AIM 3. Proteins that correlate with pre-cancer and cancer lesions will be purified and sequenced, and recombinant proteins made (for novel proteins) in Aim 4. Antibodies to the unique proteins will be used in Aim 5 to develop SELDI immunoassays for quantitation of the cancer-associated proteins in body fluids. Since the same platform is used for discovery, identification, and diagnostic assay development, the SELDI technology has a distinct advantage over other existing proteomic technologies. It is expected that either a SELDI protein profiling or SELDI immunoassay will be developed that will improve the early detection of prostate and breast cancer.