Models of Pancreatic Cancer: Understanding Disease Progression

  • Laleh G. Melstrom
  • Paul J. Grippo
Part of the M. D. Anderson Solid Tumor Oncology Series book series (MDA)

This book focuses on pancreatic cancer, which is a highly aggressive cancer that kills more than half of all of its victims within 6 months after the initial diagnosis. This dismal prognosis is due to late diagnosis, an incomplete knowledge of the pathways that generate invasive and metastatic disease, and a lack of efficacious therapies. Since patients present at such a late stage, it is extremely difficult to improve our understanding of markers of early detection, causative genetic events, and effective targets for treatment. Thus, investigations must initially concentrate on modeling systems that recapitulate the human disease at both the cellular and tissue levels. It is these systems that shed light onto the etiology of pancreatic cancer and provide the means of experimentation aimed at improving overall patient survival. Hence, the theme of this chapter is on models of pancreatic cancer and how these models help address important issues in this field of research.

One of the most pressing needs in regard to pancreatic cancer research is understanding the transitional step between PanIN development and invasive disease. Herein lies the key between early lesions and lethal cancer-identifying the causative genetic events that can serve as targets for earlier detection, chemoprevention, and therapy. Unfortunately, these types of evaluations in humans are restricted by presentation of this disease at a very late stage (metastasis). To begin unraveling the genetic alterations and epigenetic contributions that promote progression to cancer, a variety of modeling systems are needed. These models can be used in various applications, but for the sake of this chapter, attention is focused on the in vitro, ex vivo, and in vivo models of pancreatic precancer and cancer that highlight various aspects of the invasive phenotype in humans. A brief discussion of many of these models will help guide investigations focused on understanding the progression from precancer to adenocarcinoma and how particular models can suit a specific analysis.

Many of these models help address critical issues regarding the invasive nature of pancreatic cancer while providing the means with which to assess early detection schemes and evaluate novel chemoprevention and anticancer compounds. This chapter is divided into four broad sections: ( 1 ) pancreatic cancer cells in culture, ( 2 ) subcutaneous/orthotopic xenografts, ( 3 ) chemically induced rodents, and ( 4 ) genetically engineered mice.


Pancreatic Cancer Acinar Cell Pancreatic Cancer Cell Pancreatic Adenocarcinoma Pancreatic Ductal Adenocarcinoma 
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© Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Laleh G. Melstrom
    • 1
  • Paul J. Grippo
    • 2
  1. 1.Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  2. 2.Robert H. Lurie Comprehensive Cancer Center, Feinberg School of MedicineNorthwestern UniversityChicagoUSA

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