Treatment May Speed Prostate Cancer
Study Shows Hormone Therapy Can Make Prostate Cancer More Deadly
"We'd all like to find a silver bullet that attacks one thing but does not hurt anything else. The problem is there is always collateral damage," Nieh tells WebMD.
Chang's team demonstrated the opposite effects of androgen receptors in cell-culture studies and in studies of prostate-cancer-prone mice that lacked androgen receptors only in their prostate epithelial cells. These mice had much more aggressive cancer, apparently because they lost the ability to respond to the cancer-inhibiting effects of androgens.
The researchers also point to studies of prostate glands removed from men with prostate cancer. There were significantly fewer androgen receptors in metastatic prostate cancers than in early prostate cancers or in normal prostate cells.
Nieh notes that human studies will be needed to confirm the suggestion that the cancer-stimulating effect of hormone therapy explains why the treatment often fails after succeeding at first. And he says that even if hormone therapy does stimulate cancer, its inhibitory effect is more important for some patients.
"The idea of continuous hormone therapy for very advanced prostate cancer has been with us for 60 years," Nieh says. "Patients with bone metastases and extensive disease probably have much more of the stromal part of the prostate, the part that is stimulated by androgen. So they well respond better to the cancer-inhibiting aspect of hormone treatment than to any cancer-stimulating aspect."
But the Chang team's mouse studies suggest that hormone therapy may exert a stronger effect on stromal cells early in the course of disease.
Nieh points to clinical trials of intermittent hormone therapy, in which patients go off treatment from time to time. The idea is to lessen the side effects of the treatment and to extend its anticancer effect.
"With intermittent hormone therapy, animal studies suggest you may be getting a balance between the inhibitory and stimulatory effects on the cancer, whereas continuous hormone therapy drives out the inhibitory effect and you are left with the stimulatory effect," he says. "We really won't know in humans for at least four or five years because the trial is just now being done."