Featured Research

from universities, journals, and other organizations

Why Prostate Cancer Patients Fail Hormone Deprivation Therapy

Date:
January 15, 2009
Source:
Johns Hopkins Medical Institutions
Summary:
The hormone deprivation therapy that prostate cancer patients often take gives them only a temporary fix, with tumors usually regaining their hold within a couple of years. Now, researchers have discovered critical differences in the hormone receptors on prostate cancer cells in patients who no longer respond to this therapy.

The hormone deprivation therapy that prostate cancer patients often take gives them only a temporary fix, with tumors usually regaining their hold within a couple of years. Now, researchers at Johns Hopkins have discovered critical differences in the hormone receptors on prostate cancer cells in patients who no longer respond to this therapy.

The findings, reported in the Jan. 1 issue of Cancer Research, could lead to a way to track disease progression, as well as new targets to fight prostate cancer.

Prostate cancer cells rely on androgens, male hormones that include testosterone, to survive and grow, explains Jun Luo, Ph.D., an assistant professor at Johns Hopkins' James Buchanan Brady Urological Institute. Since 1941, doctors have taken advantage of this dependency to battle prostate cancer by depriving patients of androgens, either by castration or chemical methods. For most patients, this hormone deprivation therapy causes tumors to shrink, sometimes dramatically. However, it's never a cure—tumors eventually regrow into a stronger form, becoming resistant to this and other forms of treatment.

Seeking the reason why this therapy eventually fails, Luo and his colleagues at the Johns Hopkins University School of Medicine, the University of Washington and Puget Sound VA Medical Center looked to a key player: the androgen receptors on prostate cancer cells.

Using a large database, the researchers searched for variations of the nucleic acid RNA that prostate cells use to create androgen receptors, eventually identifying seven RNA sequences different from the "normal" androgen receptor already known to scientists. When they looked for these sequences in cells isolated from 124 prostate cancer patients, they found over-production of these outlaw variants in prostate cancer cells taken from patients whose disease had become resistant to hormone deprivation therapy. One variation—known as AR-V7, was also prevalent in a select group of patients who had never taken hormone therapy, but whose cancer aggressively regrew after surgery to remove their tumors.

To see how androgen receptors made from AR-V7 differ from others, the researchers forced lab-grown prostate cancer cells to produce only the AR-V7 sequence. Unlike cells with other androgen receptors, those with only AR-V7 receptors acted as if they were continually receiving androgens—turning on at least 20 genes that rely on androgens for activation—even though no androgens were present.

The results suggest that hormone therapy might encourage prostate cancer cells to overproduce the AR-V7 receptors over time, leading them to survive and grow aggressively even without androgens, explains Luo. In some patients, he adds, AR-V7 receptors might already be prevalent even without hormone therapy, predisposing them to an already-aggressive form of prostate cancer that won't respond as well to hormone deprivation therapy.

"We may eventually be able to develop an assay to test for this androgen receptor variant, giving us a way to test which patients are good candidates for hormone deprivation therapy and providing a way to monitor disease progression in patients already on this therapy," Luo says.

Examining the differences between AR-V7 and other androgen receptor variants may also provide researchers with new ideas to develop prostate cancer-fighting pharmaceuticals, he adds.

Other researchers who contributed to this study include Rong Hu, Thomas A. Dunn, Shuanzeng Wei, Sumit Isharwal, Robert W. Veltri, Elizabeth Humphreys, Misop Han, Alan W. Partin, William B. Isaacs and G. Steven Bova, all of the Johns Hopkins University School of Medicine; and Robert L. Vessella of the University of Washington and Puget Sound VA Medical Center.

This research was funded by a grant from the David H. Koch Foundation.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Cite This Page:

Johns Hopkins Medical Institutions. "Why Prostate Cancer Patients Fail Hormone Deprivation Therapy." ScienceDaily. ScienceDaily, 15 January 2009. <www.sciencedaily.com/releases/2008/12/081231005301.htm>.
Johns Hopkins Medical Institutions. (2009, January 15). Why Prostate Cancer Patients Fail Hormone Deprivation Therapy. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2008/12/081231005301.htm
Johns Hopkins Medical Institutions. "Why Prostate Cancer Patients Fail Hormone Deprivation Therapy." ScienceDaily. www.sciencedaily.com/releases/2008/12/081231005301.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. Video provided by Newsy
Powered by NewsLook.com
House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Uganda on Alert for Ebola but No Confirmed Cases

Uganda on Alert for Ebola but No Confirmed Cases

AFP (July 31, 2014) Uganda's health minister said on Thursday that there are no confirmed cases of Ebola in the country, but that it remained on alert for cases of the deadly virus. Uganda has suffered Ebola outbreaks in the past, most recently in 2012. Duration: 00:59 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins