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Cancer Lett. 2014 Mar 1;344(1):1-12. doi: 10.1016/j.canlet.2013.10.010. Epub 2013 Oct 22.

One mouse, one patient paradigm: New avatars of personalized cancer therapy.

Author information

1
Morsani College of Medicine, Department of Pathology and Cell Biology, Tampa, FL 33612, USA.
2
Morsani College of Medicine, Department of Pathology and Cell Biology, Tampa, FL 33612, USA; Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. Electronic address: vdave@health.usf.edu.

Abstract

Over the last few decades, study of cancer in mouse models has gained popularity. Sophisticated genetic manipulation technologies and commercialization of these murine systems have made it possible to generate mice to study human disease. Given the large socio-economic burden of cancer, both on academic research and the health care industry, there is a need for in vivo animal cancer models that can provide a rationale that is translatable to the clinic. Such a bench-to-bedside transition will facilitate a long term robust strategy that is economically feasible and clinically effective to manage cancer. The major hurdles in considering mouse models as a translational platform are the lack of tumor heterogeneity and genetic diversity, which are a hallmark of human cancers. The present review, while critical of these pitfalls, discusses two newly emerging concepts of personalized mouse models called "Mouse Avatars" and Co-clinical Trials. Development of "Mouse Avatars" entails implantation of patient tumor samples in mice for subsequent use in drug efficacy studies. These avatars allow for each patient to have their own tumor growing in an in vivo system, thereby allowing the identification of a personalized therapeutic regimen, eliminating the cost and toxicity associated with non-targeted chemotherapeutic measures. In Co-clinical Trials, genetically engineered mouse models (GEMMs) are used to guide therapy in an ongoing human patient trial. Murine and patient trials are conducted concurrently, and information obtained from the murine system is applied towards future clinical management of the patient's tumor. The concurrent trials allow for a real-time integration of the murine and human tumor data. In combination with several molecular profiling techniques, the "Mouse Avatar" and Co-clinical Trial concepts have the potential to revolutionize the drug development and health care process. The present review outlines the current status, challenges and the future potential of these two new in vivo approaches in the field of personalized oncology.

KEYWORDS:

18-fluorodeoxyglucose-positron emission tomography; 18FDG-PET; APL; Acute Promyelocytic Leukemia; Co-clinical Trial; Drug discovery; FDA; GEMMs; Genetically engineered mouse models; HDAC; MTA; Material Transfer Agreement; Mouse Avatars; NOD scid gamma; NSCLC; NSG; PDTX; Personalized medicine; Xenograft models; genetically enginereed mouse models; histone deacetylase; non-small cell lung cancer; patient-derived tumor xenograft; the food and drug administration

PMID:
24157811
PMCID:
PMC4092874
DOI:
10.1016/j.canlet.2013.10.010
[Indexed for MEDLINE]
Free PMC Article
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