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Experimental Therapeutics, Preclinical Pharmacology |
Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755 [N. S., C. R. W., R. R., M. R. F., M. B. S.]; Ligand Pharmaceuticals Inc., San Diego, California 92121 [W. W. L., R. A. H.]; and Lilly Research Laboratories, Indianapolis, Indiana 46285 [A. L. G., T. A. G., A. D. P.]
The selective estrogen receptor modulator arzoxifene and the rexinoid LG 100268 were active not only as single agents for prevention and treatment of breast cancer in the rat model that uses nitrosomethylurea as the carcinogen but also showed striking synergy, both preventively and therapeutically, in a series of six experiments with a total of 465 rats. Mechanistic studies in cell culture reported here suggest that enhancement of stromal-epithelial interactions may contribute to this synergy. The possible clinical use of the combination of arzoxifene and LG 100268 for prevention of breast cancer in women at high risk, for treatment of women in the adjuvant setting, or for treatment of end-stage disease should now be considered.
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