Arzoxifene: the development and clinical outcome of an ideal SERM.
Hormone-sensitive tumours are among the most common cancers in women. Specific inhibition of the estrogen receptor by selective estrogen receptor downregulators or selective estrogen receptor modulators (SERMs) is effective for the treatment of breast and endometrial cancers and may be used for the prevention of breast cancer. Due to differential recruitment of co-activators and corepressors, SERMs are tissue specific and may have antiestrogenic effects in some tissues, with estrogen agonist activity in others. The ideal SERM would have antiestrogenic effects on the breast and endometrium, but pro-estrogenic effects on bone and lipids. The SERM, arzoxifene (LY-353381.HCl) meets all of these criteria. This review summarises the development, preclinical studies and the clinical outcome of arzoxifene and places it in context with other modalities in the treatment of hormone receptor-positive tumours.
Munster
Pamela N
PN
Interdisciplinary Oncology Program, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA. Munstepn@moffitt.usf.edu
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D010880:Piperidines / Q000737:chemistry / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000639:trends*; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry / Q000627:therapeutic use*; D013876:Thiophenes / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome
D010880:Piperidines; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; C115121:LY 353381