Steroid hormone antagonists

These agents block hormone-mediated effects usually at the level of their receptors. Antagonists for oestrogens, progestins, and androgens have been developed. The most extensive experience relates to the use of the anti-oestrogen, tamoxifen, in the treatment of breast cancer. Tamoxifen binds to the oestrogen receptor and blocks the effects of endogenous oestrogens. Responses are more likely to occur in tumours that are oestrogen receptor-positive.

Tamoxifen incompletely blocks the trophic actions of oestrogen and can demonstrate partial agonist activity, especially when endogenous oestrogens are low. More potent 'pure' anti-oestrogens have therefore been developed, such as ICI182780 (Faslodex), which is a 7-alkyl amide analogue of oestradiol and completely blocks the transcrip-tional activity of the oestrogen receptor (by preventing receptor dimerization and shuttling). This drug produces clinical responses in patients with both acquired and inherent resistance to tamoxifen.

However, pure anti-oestrogens may have more detrimental effects on bones and blood vessels than the partial agonist tamoxifen. Attention has therefore focused on Selective oEstrogen-Receptor ModulatorS (SERMS), such as raloxifine, which have target-site specificity for their anti-oestrogenic activity.

Anti-androgens such as flutamide and casodex have clinical efficacy in the treatment of prostatic cancer. Anti-progestins such as RU-486 and onapristone have been used against breast and endometrial cancer.

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