Abstract
As cancer has become increasingly prevalent, cancer prevention research has evolved towards placing a greater emphasis on reducing cancer deaths and minimizing the adverse consequences of having cancer. 'Precision cancer prevention' takes into account the collaboration of intrinsic and extrinsic factors in influencing cancer incidence and aggressiveness in the context of the individual, as well as recognizing that such knowledge can improve early detection and enable more accurate discrimination of cancerous lesions. However, mouse models, and particularly genetically engineered mouse (GEM) models, have yet to be fully integrated into prevention research. In this Opinion article, we discuss opportunities and challenges for precision mouse modelling, including the essential criteria of mouse models for prevention research, representative success stories and opportunities for more refined analyses in future studies.
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Acknowledgements
The authors are grateful to colleagues who provided thoughtful comments on this article, including N. Crawford, A. Dannenberg, R. Drapkin, E. Gelmann, J. Green, S. Hanash, K. Hunter, C. Kemp, K. Olive, K. Reilly, D. Threadgill and M. Shen. Research in the C.A.-S. laboratory is supported in part by funding from the US National Cancer Institute (CA154293, CA0141535 and CA084294). C.L. is supported by the Swiss National Science Foundation (PBBSP3_146959 and P300P3_151158). A.D. is supported in part by the US National Center for Advancing Translational Sciences, National Institutes of Health, Grant Number UL1 TR000040. C.A.-S. is an American Cancer Society research professor supported in part by a generous gift from the F. M. Kirby Foundation.
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Research funding from LabCorp Patent to CAS, which covers our work on biomarkers of indolent prostate cancer. CU Invention report 3000 PCT application # PCT/US13/55469, Publication #: WO/2014/028907 entitled: Diagnostic markers of indolent prostate cancer. Priority filing date: 16 August 2012.
Glossary
- Autochthonous mouse models
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Models in which tumours arise de novo in the whole organism, as exemplified by genetically engineered mouse (GEM) models.
- Humanized mouse models
-
Mice engineered to harbour human genes of interest.
- Non-autochthonous mouse models
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Models in which tumours are engrafted into host organisms, as exemplified by patient-derived xenograft (PDX) models.
- Precision medicine
-
Customization of health care with medical decisions and practices tailored to the individual patient.
- Precision mouse modelling
-
Use of validated and optimized mouse models for prevention research.
- Precision prevention
-
Prevention strategies that incorporate precision medicine approaches and consider an individual's unique risk profile.
- Primary prevention
-
Prevention of cancer occurrence and reduction of the risk of cancer in the general population. Includes identification of hazards that promote disease or increase the risk of disease and reduction in exposure to such hazards.
- Secondary prevention
-
Reduction of the impact of cancer after it has occurred and control of cancer progression or risk of progression. Includes early detection and early intervention as well as adoption of lifestyles to prevent progression or recurrence.
- Tertiary prevention
-
Reduction of the impact of cancer to ensure a longer and better quality of life. Includes chronic disease management, but excludes cancer treatment.
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Le Magnen, C., Dutta, A. & Abate-Shen, C. Optimizing mouse models for precision cancer prevention. Nat Rev Cancer 16, 187–196 (2016). https://doi.org/10.1038/nrc.2016.1
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