Jay Hanas, Adjunct Professor of Surgery and Professor of Biochemistry & Molecular Biology at the University of Oklahoma Health Science Center (OUHSC), recently received a three year grant award from the Oklahoma Center for the Advancement of Science and Technology (OCAST) for studies on the Proteomic Analysis of Pancreatic Cancer. These studies should lead to the identification of therapeutic targets for pancreatic cancer as well as a much needed blood test for this disease. Co-principal investigators on this project include Russell Postier, Megan Lerner, Phillip Moyer, Stan Lightfoot,  Zoltan Laszik, and Daniel Brackett all from OUHSC as well as Emmanuel Petricoin from the National Cancer Institute and Willem Windig from Eigenvector Research, Inc.
 

 Pancreatic cancer is very difficult to detect in its early stages and subsequent treatment of the advanced malignancy is usually unsuccessful. It is important therefore to understand the underlying mechanisms of this cancer as well as to identify protein biomarkers for the various stages of this disease. These markers can be exploited to allow earlier diagnosis and treatment. The major goals of this proposal are to elucidate the tumorigenic mechanisms of pancreatic cancer at the protein level, to identify and analyze protein biomarkers characteristic of all stages of this disease, and to utilize these biomarkers to aid in the diagnosis and treatment of pancreatic cancer. The overall hypothesis of this study is that the mechanisms of disease progression leading to pancreatic cancer (as analyzed by comparing normal pancreas tissue, pancreatitis tissue, neoplasia, and pancreatic cancer tissue) will be manifested in unique patterns of gene expression which are largely reflected in cell phenotypes; these phenotypes are determined by the specificity, expression, modification, and function of proteins. If the proteins unique to a given pathological state can be identified and analyzed, then this information will lead to better understanding of the disease process and result in better diagnostic and therapeutic endpoints. We present evidence that a large number of protein expression changes occur in pancreatitis and pancreatic cancer in rodents and humans relative to normal pancreatic tissue. This may reflect the previously observed large number of gene changes seen in pancreatic cancer. This cancer is believed to harbor the most diverse cancer-causing mechanisms of any tumor. This extreme diversity indicates that global analysis of gene expression should yield significant information on the progression of this disease. In the present proposal, we will utilize proteomic/mass spectrometry approaches to 1) develop a much-needed blood test for pancreatic cancer, 2) identify protein biomarkers characteristic of pancreatic cancer neoplasia, and pancreatitis using whole tissue as well as microdissected tissue, 3) perform ligand-binding studies on known mediators of pancreatic cancer (e.g. NF-kappa B) in order to screen for inhibitory drugs. These studies should lead to the development of new diagnostic and treatment regimens of critical need to pancreatic cancer patients and their families.