Arzoxifene: the development and clinical outcome of an ideal SERM

Abstract

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.