Project Summary Abstract All projects in this ARTNet application will use deidentified human specimens for research directed at understanding acquired resistance to therapy in pancreatic ductal adenocarcinoma. In order to provide the necessary specimens, a Tissue Core has been developed in cooperation with and under the auspices of the University of Nebraska Medical Center (UNMC) Tissue Bank, with the goal of providing a coordinated and centralized core dedicated to procuring, processing and distributing biological specimens and associated de- identified clinical data. The Rapid Autopsy Program (RAP) core facility stores normal, benign (i.e. acute and/or chronic fibrosing pancreatitis) and malignant pancreatic tissues (including both primary and metastatic pancreatic carcinomas as well as neuroendocrine tumors) and peripheral blood lymphocytes, plasma and serum from patients undergoing surgical procedures for pancreatic malignancies and from deceased patients with a history of pancreatic cancer (rapid autopsy). Non-cancer donor whole pancreata, spleen, duodenum, liver, lung, muscle, lymph node and adrenal tissue are also collected in collaboration with local organ procurement agencies. The RAP biorepository also coordinates with surgery and oncology, as well as several well-established UNMC patient monitoring programs, such as the PCDC and PCCR, to develop robust longitudinal collections of pre, early, and end-stage tissue and biofluid sample sets. Importantly, the currently archived samples available from the rapid autopsy program are a UNMC-based resource representing the exact sample sets necessary to investigate acquired resistance in PDAC disease and continued growth of the resource will only serve to enhance UNMC’s ability to study disease resistance. The core also maintains a cache of various resources available to all cancer investigators, such as disease and normal TMAs, donor sample sequence analysis and fresh tissue acquisition. The bank includes a mechanism for database management and specimen distribution (Freezerworks) and a uniform system of prioritization of requested materials has been defined and used by the Tissue Bank Oversight Committee. This core facility is intended to benefit the specific research activities of the ARTNet, as well as the research activities of other scientists within and outside of UNMC who are concentrating on translational research issues and resistance mechanisms. Only specimens obtained from clinically indicated surgeries after all other diagnostic procedures have been performed will be submitted to the UNMC ARTNet tissue bank for resistance research. The specimens would otherwise be discarded or disposed. Eligible patients have the opportunity to participate by submitting written informed consent. There is no risk to the patient or compromise to the patient's care, as all the procedures performed would be performed for diagnostics regardless of the collection need. .