Development of androgen resistance in mouse mammary tumor cells can be prevented by the antiandrogen flutamide

As has been clearly demonstrated in prostate and breast cancer, progression to hormone insensitivity is a major problem responsible for the usually partial and short-lived response to antihormonal therapy. Preincubation of androgen-sensitive Shionogi mouse carcinoma cells for 15 days in the absence of androgens causes the development of complete resistance of cell growth to androgens. Of potentially important therapeutic significance is the finding that androgen sensitivity can be maintained not only by the androgen dihydrotestosterone (DHT) but also by incubation with the pure antiandrogen Flutamide-OH in the absence of androgens. Since androgen resistance is one of the main problems facing the treatment of prostate cancer, the possibility of avoiding or at least delaying the development of androgen resistance with a pure antiandrogen could well provide the basis for improving the success of therapy for this disease.