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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Veröffentlicht in:	EMBO molecular medicine Jg. 9; H. 2; S. 137 - 153
Hauptverfasser:	Kersten, Kelly, de Visser, Karin E, van Miltenburg, Martine H, Jonkers, Jos
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 01.02.2017 EMBO Press John Wiley and Sons Inc Springer Nature
Schlagworte:	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-Zugang:	Volltext
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 See the Glossary for abbreviations used in this article.
ISSN:	1757-4676 1757-4684
DOI:	10.15252/emmm.201606857