Chemoprevention of mammary carcinoma by LGD1069 (Targretin): an RXR-selective ligand.
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 ligand, can act as a highly effective and benign chemopreventive agent for mammary carcinoma.
Gottardis
M M
MM
Department of Endocrine Research, Ligand Pharmaceuticals, Inc., San Diego, California 92121, USA.
Bischoff
E D
ED
Shirley
M A
MA
Wagoner
M A
MA
Lamph
W W
WW
Heyman
R A
RA
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000077610:Bexarotene; D002273:Carcinogens; D004354:Drug Screening Assays, Antitumor; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D008770:Methylnitrosourea; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D014157:Transcription Factors / Q000819:agonists*; D014599:Uterus / Q000187:drug effects
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; D008770:Methylnitrosourea; D000077610:Bexarotene