A discovery by a scientist at the BC Cancer Agency explains why some prostate cancer tumours grow even without androgen, foiling chemical attempts to stop them. The discovery opens up possibilities for drug therapy to fight these hard-to-control tumours.
The research, by Dr. Marianne Sadar (J Biol Chem 1999;274[12]:7777-83), focused on hormone-resistant, or androgen-independent, prostate tumours. The usual treatment for metastasizing prostate cancer is withdrawal of testosterone (androgen), also known as "chemical castration." However, some cancerous prostate cells begin to grow again even without circulating testosterone. How this happens has puzzled scientists for decades. Researchers have known for some time that the growth-promoting effect of testosterone on prostate cancer cells is mediated by the androgen receptor - a protein that is switched on when it binds to testosterone. Sadar discovered that this receptor can be activated without testosterone, a process that may underlie androgen-independent tumour growth. This is occurring in a new region of the receptor, she says, by a mechanism that "we are still figuring out." She and her colleagues are now mapping the androgen receptor sites to find where the receptors are being activated. This is a first step in designing drugs to act as decoys for the receptor. Any new drug would be used in combination with conventional hormone withdrawal therapy. "When the patient is on androgen withdrawal therapy, we should be able to control the cell so that we can control androgen-independent disease," says Sadar.
Dr. Nicholas Bruchovsky, head of the BC Cancer Agency's Department of Cancer Endocrinology, says that "the loss of response to treatment is one of the major stumbling blocks that limits the effectiveness of today's therapies. Dr Sadar's discovery has opened up a whole new approach to possible cures."-[copyright sign] Heather Kent, Vancouver