Preclinical mouse models for immunotherapeutic and non-immunotherapeutic drug development for pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is in urgent need of better diagnostic and therapeutic methods due to its late diagnosis, limited treatment options and poor prognosis. Finding the right animal models to recapitulate the tumor molecular pathogenesis and tumor microenvironment (TME) complexity is critical for preclinical immunotherapeutic and non-immunotherapeutic treatment developments. In this review, we summarize and evaluate popular preclinical animal models including patient-derived xenograft models, humanized mouse models, genetically engineered mouse models, and syngeneic mouse models. Through comparisons between these models in different research settings, we hope to provide guidance in finding the most relevant preclinical models to suit various research purposes.

Keywords: Pancreatic Ductal Adenocarcinoma (PDAC); hemispleen; humanized mouse model; mouse models; xenograft.

Figure 1

Summary of the Generation of Selected GEMMs. (A) Generation of KP mouse by crossing LSL-Kras^G12D/+ mouse with Pdx1-Cre mouse; (B) Generation of KPC mouse by first crossing LSL-Kras^G12D/+ mouse with LSL-Trp53^R172H/+ mouse, then cross their offspring with Pdx1-Cre mouse. GEMMS, genetically engineered mouse models.

Figure 2

Summary of orthotopic models. (A) Experimental Scheme of orthotopic pancreatic mouse model; (B) ultrasound imaging of PDAC in the orthotopic model; (C) IVIS Imaging of PDAC generated with luciferase-containing KPC cells in the orthotopic model. PDAC, pancreatic ductal adenocarcinoma.

Figure 3

Summary of hemispleen models. (A) Experimental Scheme of hemispleen mouse model; (B) ultrasound imaging of PDAC in the hemispleen model; (C) IVIS Imaging of PDAC generated with luciferase-containing KPC cells in the hemispleen model. PDAC, pancreatic ductal adenocarcinoma.