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From Inception to Invasion: Modeling Pathways to Pancreatic Cancer

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Pancreatic Cancer

Part of the book series: M. D. Anderson Solid Tumor Oncology Series ((MDA))

Despite a relatively modest incidence, pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related deaths in the Western hemisphere (1). The reason is straightforward and sobering: with rare exception, pancreas cancer kills every patient it afflicts. The disease is not only uniformly but also rapidly lethal, largely because of delayed detection. Most patients are diagnosed too late in the course of disease progression to permit surgical intervention. Symptoms, when they occur at all, are typically vague and nonlocalizing, and there are currently no biomarkers for early detection. Radiographically evident lesions have already crossed the threshold of curability. Nevertheless, it is difficult to escape the conclusion that the improved survival seen in the first few years after surgery in the fortuitous few results from lead-time bias (2); all of these patients also eventually succumb to recurrent and/or metastatic disease. Despite increasingly aggressive surgical procedures and the use of adjuvant chemotherapies and radiation, the result is the same (3–5). Anatomy and biology conspire not only to elude early detection but also to hinder scientific inquiry. The pancreas is difficult to access and hazardous to biopsy: the organ does not forgive violation and biopsy can be fraught with the potentially dire consequences of pancreatitis.

These ineluctable truths of pancreas cancer beg the development of animal models that faithfully mimic the disease from its very inception to invasion and metastasis. In fact, driven by the ubiquity and sequelae of diabetes, genetic manipulation of the murine pancreas has a long and rich history that dates to the earliest experiments in transgenesis. Those early years formed the foundation for continuing refinements that have recently achieved notable success. These most recent attempts, specifically employing conditional activation of oncogenic K-ras, to genetically engineer pancreatic ductal adenocarcinoma in the mouse are the prescribed purview of this chapter.

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Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington, USA

    Sunil R. Hingorani MD, PhD

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  1. Sunil R. Hingorani MD, PhD
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Editors and Affiliations

  1. University of California San Diego, La Jolla, CA, USA

    Andrew M. Lowy

  2. School of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Steven D. Leach

  3. Wayne State University, Detroit, MI, USA

    Philip A. Philip

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Hingorani, S.R. (2008). From Inception to Invasion: Modeling Pathways to Pancreatic Cancer. In: Lowy, A.M., Leach, S.D., Philip, P.A. (eds) Pancreatic Cancer. M. D. Anderson Solid Tumor Oncology Series. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-69252-4_10

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