Antiandrogen ICI 176,334 does not prevent development of androgen insensitivity in S115 mouse mammary tumour cells

Many forms of endocrine therapy for steroid-sensitive tumours involve regimes of steroid agonist deprivation by administration of steroid antagonists. The partial or short-lived response to such therapy results from the inevitable progression of the tumour cells to a state of steroid insensitivity. Several cell culture systems have shown that steroid ablation results in loss of steroid sensitivity and we have used an in vitro model here to study the influence of steroid antagonists on this progression. Growth of androgen-responsive S 115 mouse mammary tumour cells in the long-term absence of steroid results in a loss of androgen-sensitivity. We have studied here the effects of the pure antiandrogen ICI 176,334 on the growth of S 115 cells and on their progression to steroid autonomy. Although a pure antiandrogen in its action on these cells with very low toxicity, it had no protective effect against loss of cellular or molecular androgen-responsive parameters. The clinical implications for endocrine therapy are discussed.