Colon cancer is one of the most common cancers worldwide and is the third most diagnosed cancer in the United States. In 2005, the American Cancer Society estimates 104,950 new cases and 56,290 related deaths for colon cancer. The basis for colon cancer development generally involves the evolution of adenomatous polyps to carcinoma. Individuals with a history of adenomatous polyps have a higher risk of developing cancer and therefore removal of these polyps should result in a reduction of colon cancer incidence. The foundation of screening for colon cancer is that detection of early stage disease as well as adenomatous polyps may help reduce the risk of the disease. Several methods are available for detection of colon cancer, including fecal occult blood testing, flexible sigmoidoscopy, double contrast barium enema and colonoscopy. However, costs, risk of complications and discomfort have limited the general use of these methods. The need for a simple blood test, with high clinical accuracy, will be a significant advancement in the management of this disease. However, there are none at present that meet the criteria for routine use. The development of more specific biomarkers for colon cancer has been urgently needed and an important focus of research for this disease. One approach to develop more specific biomarkers of cancer has been pursued by researchers at John Hopkins University and the University of Pittsburgh, focusing on changes to the nuclear architecture in cells, a hallmark of transition to cancer. Onconome, Inc. has licensed these novel nuclear matrix proteins and is developing products for the detection of these biomarkers for research and clinical use. One of the markers that have shown great promise to detect colon cancer is CCSA-4. Three distinct peptide sequences have been identified and serve as detection epitopes in separate prototype immunoassays. We propose in this Phase I application to further develop the CCSA-4 immunoassays to a "commercial-grade" that can be applied to larger studies. Specifically, we will (1) continue to characterize monoclonal antibodies to the CCSA-4 epitopes and optimize the immunoassay in order to apply it to larger clinical studies; (2) validate analytical performance of the optimized immunoassay; (3) demonstrate clinical feasibility of the optimized assay with clinical samples by showing a statistical difference between groups. These Phase I studies will serve as the foundation for further testing of a commercial assay for serum CCSA-4 as a diagnostic method for the detection of colon cancer. Development of a commercial grade Colon Cancer Specific Antigen (CCSA-4) serum assay will significantly improve the ability to detect colon cancer. Current available methods are fecal occult blood testing, flexible sigmoidoscopy, double contrast barium enema and colonoscopy. The current tests when used together miss a significant portion of cancer cases and also, falsely identify many patients as having cancer when they do not. The addition of the CCSA-4 serum assay will greatly improve current detection methods, and allow for a less invasive method for colon cancer detection
