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[Cancer Research 56, 5566-5570, December 15, 1996]
© 1996 American Association for Cancer Research
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Chemoprevention of Mammary Carcinoma by LGD1069 (Targretin): An RXR-selective Ligand

Marco M. Gottardis1, Eric D. Bischoff, Michael A. Shirley, Murriel A. Wagoner, William W. Lamph and Richard A. Heyman

Departments of Endocrine Research [M. M. G., M. A. W.], Retinoid Research [E. D. B., W. W. L., R. A. H.], and Drug Safety and Disposition [M. A. S.], Ligand Pharmaceuticals, Inc., 10255 Science Center Drive, San Diego, California 92121

Recently, 9-cis retinoic acid, a high affinity ligand for retinoic acid receptors and retinoid X-receptors (RXRs), was shown to have efficacy superior to all-trans retinoic acid as a chemopreventive agent in the N-nitroso-N-methylurea-induced rat mammary carcinoma model. To further explore the specific contribution RXR activation may play in suppression of carcinogenesis, the efficacy of LGD1069 (Targretin), an RXR-selective ligand, in the N-nitroso-N-methylurea-induced rat mammary tumor model was studied. LGD1069-treated animals showed a 90% reduction in tumor burden and tumor incidence compared with vehicle-treated rats with an efficacy similar to that achieved with tamoxifen. LGD1069 was very well tolerated during 13 weeks of chronic therapy with no classic signs of "retinoid-associated" toxicities. These data demonstrate that LGD1069, an RXR-selective lignad, can act as a highly effective and benign chemopreventive agent for mammary carcinoma.

1 To whom requests for reprints should be addressed, at Department of Endocrine Research, Ligand Pharmaceuticals, 10255 Science Center Drive, San Diego, CA 92121.

Received 9/ 4/96. Accepted 10/29/96.




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