title: GEMMs as preclinical models for testing pancreatic cancer therapies.
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.
authors.affiliation: Cancer 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.
authors.forename: Aarthi
authors.initials: A
authors.lastname: Gopinathan
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Morton
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK.
authors.forename: Duncan I
authors.initials: DI
authors.lastname: Jodrell
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK Aarthi.Gopinathan@cruk.cam.ac.uk o.sansom@beatson.gla.ac.uk.
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Sansom
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D055808:Drug Discovery; D005818:Genetic Engineering; D051379:Mice; D058990:Molecular Targeted Therapy; D010190:Pancreatic Neoplasms / Q000628:therapy*
keywords: Co-clinical trials; Drug development; Drug discovery; PDAC; Pancreatic ductal adenocarcinoma; Preclinical mouse models