Prevention and treatment of experimental breast cancer with the combination of a new selective estrogen receptor modulator, arzoxifene, and a new rexinoid, LG 100268.
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.
Suh
Nanjoo
N
Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Lamph
William W
WW
Glasebrook
Andrew L
AL
Grese
Timothy A
TA
Palkowitz
Alan D
AD
Williams
Charlotte R
CR
Risingsong
Renee
R
Farris
M Rendi
MR
Heyman
Richard A
RA
Sporn
Michael B
MB
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008770:Methylnitrosourea; D009361:Neoplasm Invasiveness; D009539:Nicotinic Acids / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D017154:Stromal Cells / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016588:Anticarcinogenic Agents; D009539:Nicotinic Acids; D010880:Piperidines; D020845:Selective Estrogen Receptor Modulators; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D016212:Transforming Growth Factor beta; D008770:Methylnitrosourea; C115121:LY 353381; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C095104:LG 100268