Animal models are crucial in preclinical efficacy testing of chemoprevention agents. The most feasible, realistic, and potentially effective target for prostate cancer chemoprevention is progression from prostatic intraepithelial neoplasia (PIN) to histologic cancer and from histologic to clinically manifest cancer. There are transgenic mouse models for prostate cancer and models for PIN, but these have not yet been fully developed and evaluated for chemoprevention studies. Human prostate cancer xenografts in mice and transplantable Dunning rat prostate carcinomas can be used to assess tumor growth inhibition. Several Dunning tumors metastasize, enabling detection of inhibition of metastases. Detection of inhibitory effects on de novo prostate cancer development requires induction of a high cancer incidence and similarity of induced tumors to human prostate carcinomas. Transgenic mice with oncogenes expressed in a prostate-specific fashion, combined chronic treatment of NBL rats with estradiol-17β and testosterone, and sequential treatment of rats with carcinogens such as N-methyl-N-nitrosourea (MNU) and chronic testosterone treatment all lead to a high incidence of prostatic adenocarcinomas. PIN occurs mostly in the former two models, and metastases are frequent in some transgenic models and the MNU-testosterone rat model. The latter model has been applied to chemoprevention agent efficacy testing. In 8 control groups, the carcinoma incidence was 77% in all accessory sex glands combined, 51% for small tumors confined to dorsolateral/anterior prostate, and 25% for large tumors of uncertain origin in the prostate area. This model was predictive of the lack of antiprostate cancer efficacy of N-(4-hydroxyphenyl)all-trans-retinamide in humans. Thus, rats given MNU and chronic testosterone represent a relevant and reliable model for efficacy testing of chemoprevention agents. In conclusion, there are now adequate animal models for prostate cancer proven to be suitable for preclinical chemoprevention studies.
Dr. Maarten C. Bosland
Department of Environmental Medicine, New York University School of Medicine
550 First Avenue, New York, NY 10016 (USA)
Tel. +1 212 951 5428, Fax +1 212 951 5424
Number of Print Pages : 5
Number of Figures : 1, Number of Tables : 1, Number of References : 17
Official Organ of the European Association of Urology
Vol. 35, No. 5-6, Year 1999 (Cover Date: May-June 1999)
Journal Editor: C.C. Schulman, Brussels
ISSN: 0302–2838 (print), 1421–993X (Online)
For additional information: http://www.karger.ch/journals/eur
Article / Publication Details
Published online: 4/16/2012
Issue release date: May–June 1999
Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 1
ISSN: 0302-2838 (Print)
eISSN: 1421-993X (Online)
For additional information: http://www.karger.com/EUR
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