Growths are able to maintain significant testosterone levels despite therapy, study finds
TUESDAY, June 3 (HealthDay News) -- U.S. researchers have uncovered new information about how metastatic prostate cancer becomes resistant to androgen-deprivation therapy, which suppresses circulating testosterone, the hormone that promotes prostate cancer growth.
Androgen therapy, which involves the use of surgical castration or medical castration with testosterone-blocking drugs, does extend survival time for patients, but it isn't a cure. Eventually, the cancer becomes resistant to androgen deprivation and continues to grow.
"We found that despite the suppression of circulating androgen levels to very low or castrate levels, metastatic prostate tumors are themselves able to maintain significant levels of testosterone, which fuels the growth of the cancer," Dr. Elahe Mostaghel, a clinical research association at Seattle's Fred Hutchinson Cancer Research Center, said in a prepared statement.
Mostaghel and colleagues found that testosterone levels in metastatic prostate tumors (cancer that's spread from the prostate to other parts of the body) from castrate men who'd just died were four times higher than in benign and cancerous prostate tissue in men with normal circulating androgen levels.
They also discovered that metastatic prostate tumor tissue contains the genetic information needed to make the proteins that produce testosterone and other androgen hormones.
"We not only found that metastatic tumor tissues have high enough androgen levels within them to support continued growth of the tumor cells, but also a critically important reason behind why those androgens are there -- the discovery that the gene pathways for synthesizing androgens from cholesterol appear to be present in the distant tumor sites. This finding will allow us to start honing in on the specific source of those androgens and how we can eliminate them," Mostaghel said.
"As we develop new drug targets, we will need to focus on enzymes that seem to be active in the tumor itself. This offers a new way of looking at hormone suppression. In addition to systemic suppression, it suggests we also need to target hormone suppression much more specifically, inside the tumor itself."
The study was published in the June 1 issue of Cancer Research.
The National Cancer Institute has more about prostate cancer treatment.
-- Robert Preidt
SOURCE: Fred Hutchinson Cancer Research Center, news release, June 1, 2008
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