Pancreatic cancer is a fatal disease resulting in nearly 30,000 deaths annually in the United States. From the time of diagnosis, the median survival ranges from 3 to 6 months, giving pancreatic cancer the most dismal prognosis of all malignancies. Some of the reasons for this discouraging outlook include the aggressive nature of pancreatic cancer, its resistance to standard chemotherapy and radiation therapy, and the inability to detect this malignancy in earlier stages. Our research group has been studying the mechanisms concerning the origins and growth regulation of pancreatic cancer with the long-range goals of designing strategies for early diagnosis and novel treatment. In preliminary studies, the candidate has discovered that the gastrointestinal peptides gastrin and CCK regulate growth of human pancreatic cancer through a unique CCK-B/gastrin-like receptor. Other investigations have documented that an endogenous peptide called opioid growth factor serves as a regulatory agent for pancreatic cancer where it represses growth through a nuclear-associated receptor, zeta. This grant hypothesizes that growth of human pancreatic cancer can be inhibited by manipulation of the regulatory peptides involved in controlling the tumorigenic events. In order to test this hypothesis, the following specific aims are proposed. 1) Study the role of regulatory peptides in growth of human pancreatic cancer, 2) Evaluate human pancreatic tissue and blood specimens to develop tumor markers for the early detection of pancreatic cancer, 3) Design clinical trials to test the efficacy of peptides, antisense oligonucleotides, or antibodies in human subjects with pancreatic cancer, and 4) Provide time to allow the candidate to understand clinical research and serve as a mentor to students and clinician scientists. These studies are part of the applicant's long-range objectives which include the understanding of the role of peptides in pancreatic cancer and to extend her basic science research into therapeutic clinical trials in human subjects.
|Smith, Jill P; Conter, Robert L; Bingaman, Sandra I et al. (2004) Treatment of advanced pancreatic cancer with opioid growth factor: phase I. Anticancer Drugs 15:203-9|
|Smith, Jill P; Verderame, Michael F; Ballard, Elizabeth N et al. (2004) Functional significance of gastrin gene expression in human cancer cells. Regul Pept 117:167-73|
|Smith, Jill P; Stanley, Wayne B; Verderame, Michael F et al. (2004) The functional significance of the cholecystokinin-C (CCK-C) receptor in human pancreatic cancer. Pancreas 29:271-7|
|Smith, Jill P; Verderame, Michael F; McLaughlin, Patricia et al. (2002) Characterization of the CCK-C (cancer) receptor in human pancreatic cancer. Int J Mol Med 10:689-94|