Progress in Animal Models of Pancreatic Ductal Adenocarcinoma

Abstract

As a common gastrointestinal tumor, the incidence of pancreatic cancer has been increasing in recent years. The disease shows multi-gene, multi-step complex evolution from occurrence to dissemination. Furthermore, pancreatic cancer has an insidious onset and an extremely poor prognosis, so it is difficult to obtain cinical specimens at different stages of the disease, and it is, therefore, difficult to observe tumorigenesis and tumor development in patients with pancreatic cancer. At present, no standard protocols stipulate clinical treatment of pancreatic cancer, and the benefit rate of new targeted therapies is low. For this reason, a well-established preclinical model of pancreatic cancer must be established to allow further exploration of the occurrence, development, invasion, and metastasis mechanism of pancreatic cancer, as well as to facilitate research into new therapeutic targets. A large number of animal models of pancreatic cancer are currently available, including a cancer cell line-based xenograft, a patient-derived xenograft, several mouse models (including transgenic mice), and organoid models. These models have their own characteristics, but they still cannot perfectly predict the clinical outcome of the new treatment. In this paper, we present the distinctive features of the currently popular pancreatic cancer models, and discuss their preparation methods, clinical relations, scientific purposes and limitations.

Figure 1

Tetracycline-induced TetO-Cre for GEMM. A: Cre mice (TRE-Cre, also called tetO-Cre) controlled by a tetracycline-responsive element (TRE, also called tetO). C: Mice expressing a tetracycline-responsive transcriptional activator rtTA or tTA driven by a tissue-specific promoter.