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[Cancer Research 62, 6376-6380, November 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

The Retinoid X Receptor-Selective Retinoid, LGD1069, Prevents the Development of Estrogen Receptor-Negative Mammary Tumors in Transgenic Mice1

Kendall Wu, Yun Zhang, Xiao-Chun Xu, Jamal Hill, Joseph Celestino, Hee-Tae Kim, Syed K. Mohsin, Susan G. Hilsenbeck, William W. Lamph, Reid Bissonette and Powel H. Brown2

Breast Center, Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030 [K. W., Y. Z., J. H., J. C., H-T. K., S. K. M., S. G. H., P. H. B.]; Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [X-C. X.]; and Department of Retinoid Research, Ligand Pharmaceuticals, Inc., San Diego, California 92121 [W. W. L., R. B.]

Despite the effectiveness of the selective estrogen receptor (ER) modulators in preventing ER-positive breast cancer, chemopreventive agents still need to be developed for the prevention of ER-negative breast cancers. The naturally occurring retinoids are promising agents for the prevention of human cancers but are too toxic for long-term chronic use. We previously demonstrated that the chemopreventive effects of the retinoids could be separated from the toxicity by using an RXR-selective retinoid, LGD1069. The studies described here demonstrate that LGD1069 effectively suppresses ER-negative tumor development in mouse mammary tumor virus-erbB2 transgenic mice with minimal toxicity. These studies suggest that receptor-selective retinoids are promising agents for the prevention of breast cancer and that they may be particularly useful in preventing ER-negative breast cancer.




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