TY - JOUR
T1 - The mighty mouse
T2 - Genetically engineered mouse models in cancer drug development
AU - Sharpless, Norman E.
AU - DePinho, Ronald A.
N1 - Funding Information:
We thank P. Nisen, K.-K. Wong, K. Anderson, D. Hanahan, D. Frost, G. Gordon, A. Shoemaker and S. Mellis for stimulating discussions and critical reading of the manuscript. R. A. D. is an ACS Research Professor and an Ellison Medical Foundation Senior Scholar. This work was supported by grants from the Sidney Kimmel Foundation for Cancer Research (N.E.S.), the Ellison Medical Foundation (N.E.S. and R.A.D.) and the National Institutes of Health. R.A.D. is supported by the LeBow Fund to Cure Myeloma and the Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science.
PY - 2006/9
Y1 - 2006/9
N2 - 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 that more faithfully mimic the genetic and biological evolution of human cancers. Greater use of such models in target validation, assessment of tumour response, investigation of pharmacodynamic markers of drug action, modelling resistance and understanding toxicity has the potential to markedly improve the success of cancer drug development.
AB - 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 that more faithfully mimic the genetic and biological evolution of human cancers. Greater use of such models in target validation, assessment of tumour response, investigation of pharmacodynamic markers of drug action, modelling resistance and understanding toxicity has the potential to markedly improve the success of cancer drug development.
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U2 - 10.1038/nrd2110
DO - 10.1038/nrd2110
M3 - Review article
C2 - 16915232
AN - SCOPUS:33748331308
SN - 1474-1776
VL - 5
SP - 741
EP - 754
JO - Nature Reviews Drug Discovery
JF - Nature Reviews Drug Discovery
IS - 9
ER -