Prostatic cancer has long been a major affliction of men, and it is becoming more common and dangerous as the population ages. To the present time, there are no effective preventive or treatment methods for prostatic cancer. When the cancer is in its early, hormone-dependent stage, it is commonly treated by orchiectomy or chemical castration, and the androgen flutamide is sometimes administered. In the later stages of prostatic cancer, the disease becomes hormone-independent and metastasizes widely, usually metastasizing first into the skeleton. In that advanced stage of the disease, radiation is used to alleviate pain and to slow metastasis in the radiated areas, but there are no effective methods which can put prostatic cancer into remission in that stage. Thus, prostatic cancer is not only relatively common, but is refractory to treatment once the disease crosses into the hormone-independent stage.
For some time, the enzyme 5.alpha.-reductase (5AR) has been known to be important in the physiological mechanisms related to testosterone and 5.alpha.-dihydrotestosterone. It is known that 5.alpha.-dihydrotestosterone is an extremely potent androgen and it has been known or suspected that it is involved in the mechanisms of benign prostatic hyperplasia, male pattern baldness, and prostatic cancer among other disorders and diseases. One 5AR inhibitor, finasteride, is now approved in the United States and other countries for the treatment of benign prostatic hyperplasia.
Recently it has been found that there are at least two 5AR isozymes in the human, Andersson et al., Proc. Natl. Acad. Sci. USA, 87, 3640-44 (1990); Andersson et al., Nature, 354, 159-61 (1991). The two isozymes, usually called Type I and Type II, exhibit differences in their biochemical properties, genetics and pharmacology. Both isozymes are now the subject of considerable research and it has been found that Type I is more prevalent in the scalp, and that Type II is more prevalent in the prostate.
It has now been discovered that Type I 5AR is the form of the enzyme which is active in the processes by which prostatic cancer develops and metastasizes, particularly in metastasis to bone. Accordingly, it is now possible to provide methods of treatment and prevention of prostatic cancer, which are effective in the hormone-independent stage as well as the hormone-dependent stage of the disease.