Model organisms: The mighty mouse: genetically engineered mouse models in cancer drug development

@article{Sharpless2006ModelOT,
  title={Model organisms: The mighty mouse: genetically engineered mouse models in cancer drug development},
  author={Norman E Sharpless and Ronald A. DePinho},
  journal={Nature Reviews Drug Discovery},
  year={2006},
  volume={5},
  pages={741-754}
}
Deficiencies in the standard preclinical methods for evaluating potential anticancer drugs,such as xenograft mouse models, have been highlighted as a key obstacle in the translation of the major advances in basic cancer research into meaningful clinical benefits. In this article, we discuss the established uses and limitations of xenograft mouse models for cancer drug development, and then describe the opportunities and challenges in the application of novel genetically engineered mouse models… Expand
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References

SHOWING 1-10 OF 114 REFERENCES
Contributions of human tumor xenografts to anticancer drug development.
TLDR
It is taken that properly used and interpreted human tumor xenografts grown in immunodeficient mice can be useful, although not absolutely predictive of behavior in the clinic, and continue to make contributions to critical clinical development choices. Expand
Integrating pharmacology and in vivo cancer models in preclinical and clinical drug development.
TLDR
The value and limitations of xenograft models, and the role of integrating preclinical pharmacology in developing new treatments for solid tumours of childhood are reviewed. Expand
Cancer Modeling in the Modern Era Progress and Challenges
TLDR
This review highlights some of the current strategies for modeling cancer in the mouse, recent accomplishments, and key remaining challenges. Expand
Scaling down imaging: molecular mapping of cancer in mice
TLDR
Miniaturized imaging equipment and reporter probes can be used to continuously monitor in vivo tumour development, the effects of therapeutics on individual populations of cells, or even specific molecules, and might be translated into the clinic in the future to non-invasively detect and monitor treatment of human cancers. Expand
Reporter mice and drug discovery and development
TLDR
Although reporter-gene technology is in its infancy, with further refinement reporter animals could become a valuable tool in the early stages of target and lead identification and preclinical drug development. Expand
Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models.
TLDR
It is suggested that under the right framework and when panels are used, the in vitro cell line and human xenograft models may be useful in predicting the Phase II clinical trial performance of cancer drugs. Expand
Animal models for studying the action of topoisomerase I targeted drugs.
TLDR
Development of assays that identify analogues that maintain therapeutic activity in mice, but have less species differential toxicity, may provide an early screen to select compounds having greater clinical utility. Expand
Transgenic models of tumor development.
TLDR
These mice are providing insights into the effects of individual oncogenes on cellular proliferation, differentiation, and viability, as well as on oncogene cooperativity, and should prove valuable in tests of potential carcinogens, therapies, and preventive measures. Expand
Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials
TLDR
For 39 agents with both xenograft data and Phase II clinical trials results available, in vivo activity in a particular histology in a tumour model did not closely correlate with activity in the same human cancer histology, casting doubt on the correspondence of the pre-clinical models to clinical results. Expand
Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance
TLDR
It is shown that drug resistance does not develop in three tumour types treated with a potent angiogenesis inhibitor, and an unexpected finding is that repeated cycles of antiangiogenic therapy are followed by prolonged tumour dormancy without further therapy. Expand
...
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2
3
4
5
...