Animal models of pancreatic cancer and their application in clinical research

Figures & data

Table 1 Advantages and disadvantages of pancreatic cancer models

Model type	Advantages	Disadvantages
Genetically engineered mouse models	Informative for involvement of particular genetic mutations. Competent immune system. Tumors arise in the pancreas, and metastasis follows normal pattern. Tumor interacts with stroma of the same species. Allow assessment of initiating and preinvasive mechanisms. Allow assessment of novel therapeutics. Allow analysis of predisposition factors.	Costly and time-consuming to generate. All tumor cells have the same mutations (until tumors develop instability). Unless conditional models are used, genetic manipulation present from birth and in all cells.
Cell line xenografts	Quick model to establish, therefore relatively inexpensive. Readily expandable to allow high-throughput work. Allow for genetic manipulation of cells prior to and after implantation using inducible system.	Require immune suppression (except in mouse cell tumor cell line models). Stromal interactions not present as xenograft not typically orthotopic. Cell lines lack biological stability. Xenograft establishment rate is poor.
Patient-derived cell line xenografts	Quick to develop. Allow assessment of targeted therapeutics and as a means to identify patient-specific treatment. Can be serially passaged through multiple mice and maintain most features. Responsiveness to therapy can be modeled to specific mutations by sequencing xenografts.	Immune system has to be suppressed. Patient-derived cell lines display clonality (if passaged frequently) and therefore lack heterogeneity of original tumor. Expansion is limited.
Patient-derived tumor chip xenografts	Most closely resemble mutational spectrum of a patient including heterogeneity. Include stroma of human origin. Quick to develop. Allow assessment of targeted therapeutics and as a means to identify patient-specific treatment. Display three-dimensional growth characteristics. Can be serially passaged through multiple mice and maintain most features. Responsiveness to therapy can be modeled to specific mutations by sequencing tumor cells that are refractory to treatment.	Immune system has to be suppressed. Limited to biopsy samples or resectable tumors only. Limited to few replicates per tumor.
In vivo organoid models	Organoids can be cultured indefinitely and cryopreserved, allowing high-throughput analysis. Can be of mouse or human origin and generated from FNB. Orthotopic transplantation leads to PanIN and invasive PCa. Allow assessment of malignant processes of ductal cells and novel interventions. Tumors display stromal involvement. Progress in a reasonable time frame.	Costly. Require sampling of tumors to generate. Human organoids require immunosuppressed animals. High levels of necrosis in tumor samples prevents organoid generation.

Abbreviations: PanIN, pancreatic intraepithelial neoplasia; FNB, fine needle biopsies; PCac, pancreatic cancer.

Figure 1 Schematic outlining the use of PDXs to target actionable mutations identified in an individual’s pancreatic tumor and FNA samples to provide the clinician with a more informed decision on the potential efficacy of the selected therapeutic agent.

Abbreviations: PDXs, patient-derived xenografts; FNA, fine-needle aspiration.