Review ArticlesUnderstanding Disease Biology and Informing the Management of Pancreas Cancer With Preclinical Model SystemsWhittle, Martin C. PhD*; Hingorani, Sunil R. MD, PhD*†‡Author Information From the *Clinical Research Division and †Public Health Sciences Division, Fred Hutchinson Cancer Research Center; and ‡ Division of Medical Oncology, University of Washington School of Medicine, Seattle, WA Conflicts of Interest and Sources of Funding: This work was supported by the National Institutes of Health National Cancer Institute grant CA161112 and the Giles W. and Elise G. Mead Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Reprints: Sunil R. Hingorani, MD, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M5-C800, Seattle, WA 98109. E-mail: [email protected]. The Cancer Journal: 11/12 2017 - Volume 23 - Issue 6 - p 326-332 doi: 10.1097/PPO.0000000000000289 Buy Metrics Abstract Recent advances in cytotoxic therapies for pancreatic ductal adenocarcinoma (PDA) are overshadowed by stalled clinical progress of more targeted strategies, the vast majority of which have failed in clinical trials. Inability to translate preclinical promise into clinical efficacy derives, in part, from imperfect disease modeling and mismatches between preclinical and clinical study design and execution. Into these gaps fall our patients who enter the clinical trial landscape expectantly and bear the brunt of its inadequacies. If improving patient survival is paramount, then it must be acknowledged that the failure of a phase III trial represents a larger failure of all of the work that preceded it. Repeated failures suggest a need to reappraise the current preclinical-to-clinical apparatus. Exceptional models of PDA are now available to researchers, and the first steps toward a new era of success can begin with improved selection and application of these systems. We discuss the key features of the major preclinical platforms for PDA and propose a paradigm for rigorous interrogation of prospective therapies. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.