Primary Appointment

     Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Although significant advances are beginning to be made into the management of the disease, the 5- year survival rate has not improved over the past 25 years. The high mortality rate is due to the high incidence of metastatic disease at initial diagnosis, the aggressive clinical course and the failure of systemic therapies and the standard care of chemotherapeutic treatment, gemcitabine (gem) is less beneficial because of the development of resistance to gem. Therefore, there is an urgent need for improved understanding of the molecular biology of the disease. Early detection and effective treatments are the utmost needs of pancreatic cancer which could be addressed by identifying good biomarkers and molecular targets against pancreatic cancer. Microarray profiling identified that several molecules has been differentially expressed in pancreatic cancer.

     Real-time quantitative PCR and immunolocalization in tissue array validated the expression profiles of those molecules. Functional characterization was conducted by in vitro and in vivo experiments and those which increased the aggressiveness of pancreatic cancer on over-expression and decreased the pancreatic cancer cell growth were considered as good therapeutic targets. Identification of targets is of limited value without a means to manipulate the targets. Hence, experimental therapeutic intervention was carried out by means of pharmacological drugs, siRNA, peptides and antibodies against the therapeutic targets. Manipulation of molecules to further sensitize the tumors for standard chemotherapeutic drugs was also tested. Molecular intervention of Adrenomedullin and Anterior gradient-2 proved to be very successful in reducing the aggressiveness of pancreatic cancer and increasing the sensitivity of the chemotherapeutic drugs. Further validation of new molecules is underway. Validation of candidate biomarkers for early detection of pancreatic cancer is also ongoing.

     Diabetes mellitus is a prelude for pancreatic cancer; metastasis and cachexia are associated with end-stage of the disease. The mechanism behind the development of these two conditions is not understood. Difference in glucose intolerance, metastasis and cachexia formation in tumors developed with different pancreatic cancer cell lines suggested a way for differential expression pattern of genes which is under construction now.

Institutional Committee Activities

Last updated: 12/18/2012