Genetically engineered mouse models in oncology research and cancer medicine

Genetically engineered mouse models (GEMMs) have contributed significantly to the field of cancer research. In contrast to cancer cell inoculation models, GEMMs develop de novo tumors in a natural immune‐proficient microenvironment. Tumors arising in advanced GEMMs closely mimic the histopathologica...

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Bibliographic Details
Published in:EMBO molecular medicine Vol. 9; no. 2; pp. 137 - 153
Main Authors: Kersten, Kelly, de Visser, Karin E, van Miltenburg, Martine H, Jonkers, Jos
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.02.2017
EMBO Press
John Wiley and Sons Inc
Springer Nature
Subjects:
Animal models
Animals
Animals, Genetically Modified
Biology
Cancer
Cancer therapies
Cell adhesion & migration
Cell culture
Clinical trials
CRISPR
Disease Models, Animal
Drug resistance
EMBO03
Extracellular matrix
Fibroblasts
Genes
Genetic engineering
genetically engineered mouse models
Genomes
Genomics
Grants
Humans
Immune system
Immunotherapy
Inoculation
Laboratories
Medical Oncology - methods
Medical research
Metastases
Metastasis
Mice
Mutation
Neoplasms - pathology
Neoplasms - therapy
Oncology
Patients
Review
Rodents
Stem cells
Therapeutic applications
therapy
tumor microenvironment
Tumors
Netherlands
cancer
genetically engineered mouse models
tumor microenvironment
metastasis
therapy
ISSN:1757-4676, 1757-4684
Online Access:Get full text
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Summary:Genetically engineered mouse models (GEMMs) have contributed significantly to the field of cancer research. In contrast to cancer cell inoculation models, GEMMs develop de novo tumors in a natural immune‐proficient microenvironment. Tumors arising in advanced GEMMs closely mimic the histopathological and molecular features of their human counterparts, display genetic heterogeneity, and are able to spontaneously progress toward metastatic disease. As such, GEMMs are generally superior to cancer cell inoculation models, which show no or limited heterogeneity and are often metastatic from the start. Given that GEMMs capture both tumor cell‐intrinsic and cell‐extrinsic factors that drive de novo tumor initiation and progression toward metastatic disease, these models are indispensable for preclinical research. GEMMs have successfully been used to validate candidate cancer genes and drug targets, assess therapy efficacy, dissect the impact of the tumor microenvironment, and evaluate mechanisms of drug resistance. In vivo validation of candidate cancer genes and therapeutic targets is further accelerated by recent advances in genetic engineering that enable fast‐track generation and fine‐tuning of GEMMs to more closely resemble human patients. In addition, aligning preclinical tumor intervention studies in advanced GEMMs with clinical studies in patients is expected to accelerate the development of novel therapeutic strategies and their translation into the clinic. Graphical Abstract Tumors arising in advanced genetically engineered mouse models (GEMMs) mimic their human counterparts including heterogeneity and spontaneous metastases. This review provides a sweeping overview of the field and a discussion of their bright future.
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See the Glossary for abbreviations used in this article.
ISSN:1757-4676
1757-4684
DOI:10.15252/emmm.201606857