title: The combination of the rexinoid, LG100268, and a selective estrogen receptor modulator, either arzoxifene or acolbifene, synergizes in the prevention and treatment of mammary tumors in an estrogen receptor-negative model of breast cancer.
abstract: OBJECTIVE
  We tested whether a selective estrogen receptor modulator (SERM) and a rexinoid are active for prevention and treatment in the mouse mammary tumor virus-neu mouse model of estrogen receptor-negative breast cancer.
  
  
  METHODS
  For prevention, mice were fed a powdered control diet, the SERM arzoxifene (Arz, 20 mg/kg diet), the rexinoid LG100268 (268, 30 mg/kg diet), or the combination for 60 weeks. In a second prevention study, mice were fed Arz (6 mg/kg diet), 268 (30 mg/kg diet), the combination of Arz and 268, the SERM acolbifene (Acol, 3 mg/kg diet), or the combination of Acol and 268 for 52 weeks. For the treatment studies, mice with tumors were fed combinations of a SERM and 268 for 4 weeks.
  
  
  RESULTS
  The rexinoid 268 and the SERMs Arz and Acol, as individual drugs, delayed the development of estrogen receptor-negative tumors. Moreover, the combination of a SERM and 268 was strikingly synergistic, as no tumors developed in any mouse fed the combination of 268 and a SERM. Moreover, this drug combination also induced significant tumor regression when used therapeutically. These drugs did not inhibit transgene expression in vitro or in vivo, and the combination of Arz and 268 inhibited proliferation and induced apoptosis in the tumors.
  
  
  CONCLUSIONS
  The combination of a rexinoid and SERM should be considered for future clinical trials.
authors.affiliation: Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Liby
authors.forename: Mara
authors.initials: M
authors.lastname: Rendi
authors.forename: Nanjoo
authors.initials: N
authors.lastname: Suh
authors.forename: Darlene B
authors.initials: DB
authors.lastname: Royce
authors.forename: Renee
authors.initials: R
authors.lastname: Risingsong
authors.forename: Charlotte R
authors.initials: CR
authors.lastname: Williams
authors.forename: William
authors.initials: W
authors.lastname: Lamph
authors.forename: Fernand
authors.initials: F
authors.lastname: Labrie
authors.forename: Stan
authors.initials: S
authors.lastname: Krajewski
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Xu
authors.forename: Heetae
authors.initials: H
authors.lastname: Kim
authors.forename: Powel
authors.initials: P
authors.lastname: Brown
authors.forename: Michael B
authors.initials: MB
authors.lastname: Sporn
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D009539:Nicotinic Acids / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D015996:Survival Rate; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D009539:Nicotinic Acids; D010880:Piperidines; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C012121:ritetronium; C115121:LY 353381; C095104:LG 100268