GEMMs as preclinical models for testing pancreatic cancer therapies

Gopinathan, A., Morton, J. P. , Jodrell, D. I. and Sansom, O. J. (2015) GEMMs as preclinical models for testing pancreatic cancer therapies. Disease Models and Mechanisms, 8(10), pp. 1185-1200. (doi:10.1242/dmm.021055) (PMID:26438692) (PMCID:PMC4610236)

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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)-KrasG12D; LSL-Trp53R172H; 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Morton, Dr Jennifer and Sansom, Professor Owen
Authors: Gopinathan, A., Morton, J. P., Jodrell, D. I., and Sansom, O. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Disease Models and Mechanisms
Publisher:The Company of Biologists Ltd.
ISSN:1754-8403
ISSN (Online):1754-8411
Copyright Holders:Copyright © 2015 The Company of Biologists Ltd
First Published:First published in Disease Models and Mechanisms 8(10):1185-1200
Publisher Policy:Reproduced under a Creative Commons License

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