Related Experiment Video
Updated: Apr 1, 2026
An Orthotopic Resectional Mouse Model of Pancreatic Cancer
Published on: September 24, 2020
GEMMs as preclinical models for testing pancreatic cancer therapies
Aarthi Gopinathan1, Jennifer P Morton2, Duncan I Jodrell3
1Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK Aarthi.Gopinathan@cruk.cam.ac.uk o.sansom@beatson.gla.ac.uk.
Abstract:
Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs), the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the first stages of the drug development pipeline, prior to their transition to the clinical arena. GEMMs carry mutations in genes that are associated with specific human diseases and they can thus accurately mimic the genetic, phenotypic and physiological aspects of human pathologies. Here, we discuss different GEMMs of human pancreatic cancer, with a focus on the Lox-Stop-Lox (LSL)-Kras(G12D); LSL-Trp53(R172H); Pdx1-cre (KPC) model, one of the most widely used preclinical models for this disease. We describe its application in preclinical research, highlighting its advantages and disadvantages, its potential for predicting clinical outcomes in humans and the factors that can affect such outcomes, and, finally, future developments that could advance the discovery of new therapies for pancreatic cancer.
Insights
Genetically engineered mouse models (GEMMs) are crucial for advancing pancreatic cancer research. The KPC mouse model offers a valuable preclinical tool for developing novel pancreatic cancer therapies.
Area of Science:
- Oncology
- Genetics
- Translational Medicine
Background:
- Pancreatic ductal adenocarcinoma has a poor prognosis and lacks effective treatments.
- Developing new therapies for pancreatic cancer is hindered by the absence of reliable preclinical models.
- Genetically engineered mouse models (GEMMs) accurately replicate human disease genetics and phenotypes.
Purpose of the Study:
- To review GEMMs for human pancreatic cancer.
- To focus on the Lox-Stop-Lox (LSL)-Kras(G12D); LSL-Trp53(R172H); Pdx1-cre (KPC) model.
- To discuss the KPC model's utility in preclinical research and its predictive potential.
Main Methods:
- Review of existing literature on GEMMs for pancreatic cancer.
- Detailed examination of the KPC mouse model.
- Analysis of KPC model's advantages, disadvantages, and clinical predictive value.
Main Results:
- GEMMs, particularly the KPC model, are essential for pancreatic cancer research.
- The KPC model accurately mimics human pancreatic cancer's genetic and phenotypic aspects.
- Factors influencing the KPC model's predictive accuracy for human outcomes are identified.
Conclusions:
- The KPC model is a widely used and valuable preclinical tool for pancreatic cancer therapy development.
- Understanding the KPC model's strengths and limitations is key to its effective application.
- Further advancements in GEMMs will accelerate the discovery of new pancreatic cancer treatments.
