UNIVERSITY OF NEBRASKA MEDICAL CENTER SPORE IN PANCREATIC CANCER

PRINCIPAL INVESTIGATOR: Michael A. Hollingsworth, Ph.D.

Project Period: 09/05/2008 – 08/31/2013

The Specialized Program of Research Excellence in Gastrointestinal (Pancreatic Cancer) will focus on translational studies that address basic and clinical issues of importance to improving the outcome of patients with pancreatic cancer. Specifically, the research projects in this program seek to: 1) develop and test novel diagnostic reagents and assays that will improve our ability to detect pancreatic cancer in its early stages; 2) develop and test novel therapeutic strategies including immunotherapy, chemotherapy, and chemoradiation therapy for patients with early and advanced pancreatic cancer; 3) undertake basic research studies in conjunction with clinical trials that will provide insight at the molecular level into the reasons for success and failure of the different strategies. The SPORE program is focused on 4 projects with the high potential translational impact, and there are 3 highly interactive cores that will continue to acquire, store, and make available a unique set of tissue samples, data (clinical, molecular, genetic, biological, pathological), reagents and resources:

Project 1:         Immunotherapy of Pancreatic Adenocarcinoma

Project 2:         Inhibitors of N-cadherin in the treatment of pancreatic cancer.

Project 3:         Biological marker(s) in the diagnosis of pancreatic cancer

Project 4:         Inhibitors of Telomerase in treatment of pancreatic adenocarcinoma

Core A:            Administration

Core B:            Pancreas Tumor SPORE Tissue Bank

Core C:            Biostatistics

PROJECTS

Project 1:  Immunotherapy of Pancreatic Adenocarcinoma

Principal Investigators: Michael A. Hollingsworth, Ph.D. and Jean Grem, M.D.

 ·     Translational Goal: Development in a preclinical setting and use of specific immunotherapy strategies that are designed to provoke effective cell mediated immune responses to pancreatic tumors and conduct a clinical trial to test these reagents.

Project 2:  Inhibitors of N-cadherin in the treatment of pancreatic cancer

Principal Investigators: Keith Johnson, Ph.D., Margaret Wheelock, Ph.D., and Jean Grem, M.D.

 ·  Translational Goal:  Evaluate the efficacy and mechanism of action of a novel therapeutic (Exherin) that inhibits activity of N-cadherin, in the treatment of pancreatic cancer.

Principal Investigators:  Surinder Batra, Ph.D., Randall Brand, M.D., and Aaron Sasson, M.D.

 ·     Translational Goal: Develop and test methods for early detection of pancreatic cancer that include novel serum diagnostic assays and early diagnosis by using a novel light imaging technology.

Project 4: Inhibitors of Telomerase in treatment of pancreatic adenocarcinoma

Principal Investigators:  Michel Ouellette, Ph.D., Jerry Shay, Ph.D., and Jean Grem, M.D.

 ·     Translational Goal: Evaluate the in vivo effects of a telomerase inhibitor, GRN163L alone and in combination with standard chemotherapy, on two human metastatic pancreatic cancer cell lines (Colo357 and MIA-PaCa-2). In a phase I/II trial, pancreatic cancer patients with locally advanced, unresectable, or metastatic disease will receive combined gemcitabine/erlotinib chemotherapy with prolonged exposure to GRN163L, and the safety and effects of GRN163L on survival and progression-free survival will be assessed.

CORES

Core A:            Administration. Director: Michael Hollingsworth, Ph.D.

Core B:            Pancreas Tumor SPORE Tissue Bank. Director: Julia Bridge M.D.

Core C:            Biostatistics. Director: Jane Meza Ph.D.

These projects and cores represent a substantial breadth of innovative research endeavor in pancreatic cancer.  Projects 1, 2 and 4 aim to develop therapeutic reagents that will be useful for early or advanced disease.  Project 3 aims to develop early diagnostic procedures.  The cores contain highly novel components.  The tumor bank (Core B) has developed a comprehensive rapid autopsy/ organ harvest protocol unlike any other in the world, which utilizes a team of 18 trained individuals to undertake complete organ harvest and processing that can be completed within two hours of death.

For more information, please contact:

Michael A. Hollingsworth, Ph.D.

Professor

University of Nebraska Medical Center

Eppley Institute for Research in Cancer and Allied Diseases

986805 Nebraska Medical Center

Omaha, NE  68198-6805

Tel: 402/559-8343

Fax: 402/559-3339

Email: mahollin@unmc.edu