Fifty-five years ago, a Chicago surgeon named Dr. Charles Huggins discovered that prostate cancer cells needed testosterone to grow. He showed that removing or blocking the action of this male sex hormone could cause prostate cancers to shrink and suppress their ability to spread. The finding brought him the Nobel Prize and made anti-testosterone therapy the standard treatment for advanced prostate cancer.
Now, Dr. Shutsung Liao, a biochemist who has been a longtime colleague of Huggins at the University of Chicago, has discovered that the relationship between prostate cancer and testosterone is not quite so simple.
The hormone may alternately feed and suppress cancer growth over the long term, Liao said. And this finding by Liao and his colleagues, reported yesterday in the Proceedings of the National Academy of Sciences, may ultimately change the way metastatic prostate cancer is treated.
In about 80 percent of patients treated with anti-testosterone therapy, the cancer disappears at first, Liao said. Unfortunately, he pointed out, the cancer almost always comes back after one to three years of the treatment, known as androgen ablation, which is done either by surgically removing the testicles or by administering a chemical that blocks hormone action.
The recurrent cancer can then grow independently of the male sex hormone, or androgen, and is thus no longer responsive to ablation therapy.
By studying human prostate cancer cells grown in laboratory dishes and implanted in mice, Liao and his colleagues, Yoshihisa Umekita, Richard A. Hiipakka and John M. Kokontis, confirmed that prostate cancer cells at first need male hormone to grow and then gradually learn to grow in the absence of the hormone, a progression that mimics what happens in patients.
But Liao's group discovered that some of these androgen-independent cells are, in fact, very sensitive to testosterone and can be killed by exposure to small amounts of the hormone.
Liao explained how this can happen. For testosterone to act on a cell, the cell must have receptors that allow the hormone to bind to it. The Chicago researchers found that after a year or more of androgen ablation, the number of receptors on the cancer cells increased greatly.
Once that had happened, the effect of testosterone on the cancer cells resulted in the production of proteins that dictate cell death instead of growth.
At this point in the cancer's growth, anti-testosterone therapy becomes counterproductive.
Pub Date: 10/15/96
