The present invention is based, at least in part, on the generation of an
animal model of pancreatic
adenocarcinoma which recapitulates the genetic and histological features of human pancreatic
adenocarcinoma, including the
initiation, maintenance, and progression of the
disease. Accordingly, the present invention provides animal models of
cancer, e.g., pancreatic
adenocarcinoma, wherein an
activating mutation of
Kras has been introduced, and any one or more known or unknown tumor
suppressor genes or loci, e.g., Ink4a / Arf, Ink4a, Arf, p53,
Smad4 / Dpc, Lkb1, Brca2, or Mlh1, have been misexpressed, e.g., have been misexpressed leading to decreased expression or non-expression. The animal models of the invention may be used, for example, to identify biomarkers of
pancreatic cancer, to identify agents for the treatment or prevention of
pancreatic cancer, and to evaluate the effectiveness of potential therapeutic agents.