| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Review |


From the University of Nebraska Medical Center,* Omaha, Nebraska; the University of Texas M.D. Anderson Cancer Center,
Houston, Texas; and the Karmanos Cancer Institute,
Detroit, Michigan
Abstract
Animal models, by definition, are an approximation of reality, and their use in developing anti-cancer drugs is controversial. Positive retrospective clinical correlations have been identified with several animal models, in addition to limitations and a need for improvement. Model inadequacies include experimental designs that do not incorporate biological concepts, drug pharmacology, or toxicity. Ascites models have been found to identify drugs active against rapidly dividing tumors; however, neither ascitic nor transplantable subcutaneous tumors are predictive of activity for solid tumors. In contrast, primary human tumor xenografts have identified responsive tumor histiotypes if relevant pharmacodynamic and toxicological parameters were considered. Murine toxicology studies are also fundamental because they identify safe starting doses for phase I protocols. We recommend that future studies incorporate orthotopic and spontaneous metastasis models (syngeneic and xenogenic) because they incorporate microenvironmental interactions, in addition to confirmatory autochthonous models and/or genetically engineered models, for molecular therapeutics. Collectively, murine models are critical in drug development, but require a rational and hierarchical approach beginning with toxicology and pharmacology studies, progressing to human primary tumors to identify therapeutic targets and models of metastatic disease from resected orthotopic, primary tumors to compare drugs using rigorous, clinically relevant outcome parameters.
This article has been cited by other articles:
![]() |
M. Sugawara, K. Okamoto, T. Kadowaki, K. Kusano, A. Fukamizu, and T. Yoshimura Inoculation of Human Tumor Cells Alters the Basal Expression but Not the Inducibility of Cytochrome P450 Enzymes in Tumor-Bearing Mouse Liver Drug Metab. Dispos., November 1, 2009; 37(11): 2244 - 2254. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. L. Roland, S. P. Dineen, K. D. Lynn, L. A. Sullivan, M. T. Dellinger, L. Sadegh, J. P. Sullivan, D. S. Shames, and R. A. Brekken Inhibition of vascular endothelial growth factor reduces angiogenesis and modulates immune cell infiltration of orthotopic breast cancer xenografts Mol. Cancer Ther., July 1, 2009; 8(7): 1761 - 1771. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Hahn, K. Fried, L. H. Hurley, and E. T. Akporiaye Orally active {alpha}-tocopheryloxyacetic acid suppresses tumor growth and multiplicity of spontaneous murine breast cancer Mol. Cancer Ther., June 1, 2009; 8(6): 1570 - 1578. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. M. Carreno, J. R. Garbow, G. R. Kolar, E. N. Jackson, J. A. Engelbach, M. Becker-Hapak, L. N. Carayannopoulos, D. Piwnica-Worms, and G. P. Linette Immunodeficient Mouse Strains Display Marked Variability in Growth of Human Melanoma Lung Metastases Clin. Cancer Res., May 15, 2009; 15(10): 3277 - 3286. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Landskroner-Eiger, B. Qian, E. S. Muise, A. R. Nawrocki, J. P. Berger, E. J. Fine, W. Koba, Y. Deng, J. W. Pollard, and P. E. Scherer Proangiogenic Contribution of Adiponectin toward Mammary Tumor Growth In vivo Clin. Cancer Res., May 15, 2009; 15(10): 3265 - 3276. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. M. Jaffee Scientifically Driven "Proof-of-Principle" Clinical Trials: Current and Future Value to Drug Development Am. Assoc. Cancer Res. Educ. Book, April 18, 2009; 2009(1): 267 - 271. [Full Text] [PDF] |
||||
![]() |
M. G. Hollingshead Antitumor Efficacy Testing in Rodents J Natl Cancer Inst, November 5, 2008; 100(21): 1500 - 1510. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Safholm, J. Tuomela, J. Rosenkvist, J. Dejmek, P. Harkonen, and T. Andersson The Wnt-5a-Derived Hexapeptide Foxy-5 Inhibits Breast Cancer Metastasis In vivo by Targeting Cell Motility Clin. Cancer Res., October 15, 2008; 14(20): 6556 - 6563. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Richmond and Y. Su Mouse xenograft models vs GEM models for human cancer therapeutics Dis. Model. Mech., September 1, 2008; 1(2-3): 78 - 82. [Full Text] [PDF] |
||||
![]() |
S. P. Dineen, K. D. Lynn, S. E. Holloway, A. F. Miller, J. P. Sullivan, D. S. Shames, A. W. Beck, C. C. Barnett, J. B. Fleming, and R. A. Brekken Vascular Endothelial Growth Factor Receptor 2 Mediates Macrophage Infiltration into Orthotopic Pancreatic Tumors in Mice Cancer Res., June 1, 2008; 68(11): 4340 - 4346. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. A. Phadke, K. S. Vaidya, K. T. Nash, D. R. Hurst, and D. R. Welch BRMS1 Suppresses Breast Cancer Experimental Metastasis to Multiple Organs by Inhibiting Several Steps of the Metastatic Process Am. J. Pathol., March 1, 2008; 172(3): 809 - 817. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |