Mouse models of pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a disease characterized by aggressive tumor biology, desmoplasia and chemoresistance. Given the insidious nature of its onset, multiple models have been developed to study progression from in situ lesions (PanIN) to PDAC in transgenic mouse models. These have been developed using known mutations that are present in human tumors including K-ras, p53, DPC4, CDNK2a, p16 and Brca2. The metastatic character of each of these models is variable and described here. Metastasis to the lymph nodes, liver and peritoneum are also prominent features of PDAC. Syngeneic models and xenograft models (i.e. orthotopic, direct xenograft and metastatic models) are also used to study primary tumor development and metastatic disease and are described.This chapter seeks to describe murine models of experimental PDAC that are currently used to investigate mechanisms of carcinogenesis and metastatic progression, individual risk factors, tumor biology aspects, mechanisms of in vivo chemoresistance, analysis of therapeutic targets and experimental therapies.