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Contributions of Human Tumor Xenografts to Anticancer Drug Development

Marlene and Stewart Greenebaum Cancer Center, and Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland

Requests for reprints: Edward A. Sausville, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Room S9D07, 22 South Greene Street, Baltimore, MD 21201. Phone: 410-328-7394; Fax: 410-328-6896; E-mail: esausville{at}umm.edu.

Abstract

Mouse models of cancer have consistently been used to qualify new anticancer drugs for study in human clinical trials. The most used models include transplantable murine tumors grown in syngeneic hosts and xenografts of human tumors grown in immunodeficient mice. For the latter systems, retrospective preclinical-clinical correlation studies are available, which suggest that improvements must be made to increase their value. Transgenic, knock-out, and knock-in mouse models and their intercrosses are more recent developments that mirror defined steps of human carcinogenesis. However, their value in predicting clinical results remains to date poorly defined. We take the position 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. (cancer Res 2006;66(7):3351-4)

Oren J. Becher and Eric C. Holland

Departments of Cancer Biology and Genetics, Surgery (Neurosurgery) and Neurology, and Pediatrics Memorial Sloan-Kettering Cancer Center New York, New York.

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