Pancreatic cancer is the 4th leading cause of cancer-related deaths in the United States and with the five- year survival rate of less than 1%, it remains the lowest of all malignancies. Reasons for the poor prognosis of pancreatic cancer include the inability to diagnose this malignancy in early stages and its resistance to standard chemotherapy. Our research group has been studying the mechanisms involving growth regulation of pancreatic cancer with the long-range goals of designing strategies for early diagnosis and treatment. We have found that growth of pancreatic cancer is in part regulated by the gastrointestinal peptides gastrin and CCK through a unique CCK receptor which has been cloned and sequenced by the PI. Since this receptor has been detected in cancerous pancreatic tissue and not in the normal pancreas, it has been called the """"""""CCK-C"""""""" receptor. Preliminary studies show that the CCK-C receptor RNA is present in the peripheral blood of patients with pancreatic cancer but not in the blood from control subjects. Additionally, an antibody raised against the cancer-associated CCK-C receptor recognizes the receptor in human cancer cells by Western analysis, ELISA assay, and by immunohistochemical experiments. This grant hypothesizes that the CCK-C receptor may be utilized as a tool for the early detection of pancreatic cancer. In order to test this hypothesis, the following specific aims are proposed: 1) Study the specificity of the CCK-C receptor for the detection of pancreatic cancer in tissues and in blood using a case series of Gl outpatients with specific presenting symptoms. 2) Investigate the stage in which the CCK-C receptor or its RNA is detectable in the peripheral blood with both an orthotopic mouse pancreatic cancer model and with blood and pancreatic juices obtained from human subjects by RT-PCR and immunocytochemistry and 3) Develop an ELISA assay for the CCK-C receptor in human plasma with selective receptor antibodies. These studies are part of the applicant's long- term goals to understand the mechanisms controlling growth of pancreatic cancer and to diagnose patients in early stage of disease to improve long-term survival.
