Navigation Links
Why prostate cancer patients fail hormone deprivation therapy
Date:12/31/2008

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 curetumors 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 variationknown 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 androgensturning on at least 20 genes that rely on androgens for activationeven 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.


'/>"/>

Contact: Christen Brownlee
cbrownlee@jhmi.edu
410-955-7832
Johns Hopkins Medical Institutions
Source:Eurekalert

Related medicine news :

1. Conventional prognostic factors fail to explain better prostate cancer survival in most Asian men
2. First biomarker discovered that predicts prostate cancer outcome
3. Frequent Prostate Screens Fail to Improve Aggressive Cancer Diagnoses
4. New male sling procedure helps prostate cancer survivors who suffer from urinary incontinence
5. Us TOO Launches National SEA Blue Campaign for Prostate Cancer Awareness Month
6. Red wine compound shown to prevent prostate cancer
7. Barbershop Talks Cut Black Mens Prostate Cancer Risk
8. Generic prostate drug helps find high-risk cancers early
9. Finasteride unlikely to induce high grade prostate cancers
10. Shrinkage of prostate led to overestimation of cancer risk in trial
11. Prostate Cancer Awareness Week to Screen Thousands
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/20/2017)... ... August 20, 2017 , ... State Farm Neighborhood Assist® ... national causes up for a $25,000 grant. If the initiative wins, Gals Lead – ... will expand into the Tri-County area of St. Mary’s, Calvert and Charles Counties. The ...
(Date:8/19/2017)... ... August 18, 2017 , ... ... a transparent, verifiable database to help the cannabis industry move towards greater legitimacy. ... to deliver a faster technology with lower fees. Paragon will build a fully ...
(Date:8/19/2017)... ... August 19, 2017 , ... Praeclarus Press has launched ... illustrations show the diversity of the breastfeeding mothers, using bright colors and ... sizes. These illustrations are also available on tote bags, notepads, smartphone cases, clocks, ...
(Date:8/19/2017)... ... 19, 2017 , ... “Congratulations! It's A Boy! God’s Gift: A Story of ... and God. “Congratulations! It's A Boy! God’s Gift: A Story of Love” is the ... New York. , Published by Christian Faith Publishing, Dale Anthony and Rachael Anthony’s new ...
(Date:8/18/2017)... ... August 18, 2017 , ... ... International, LLC (“Quick”), a highly specialized asset-light logistics provider of complex transport ... a definitive agreement to purchase Unitrans International Corporation, a division of Roadrunner ...
Breaking Medicine News(10 mins):
(Date:8/7/2017)... , Aug. 7, 2017  Endo International plc (NASDAQ: ... agreements to resolve virtually all known U.S. mesh product ... to resolve the known remaining U.S. claims at reasonable ... beginning in the fourth quarter of 2017 and continuing ... its second quarter 2017 results, the Company intends to ...
(Date:8/2/2017)... BENTON, Ky. , Aug. 2, 2017   Marshall County Hospital in ... team to proactively reduce the risk of hospital-acquired infections (HAIs). The new addition, Tru-D ... UVC light energy to kill deadly pathogens such as C. diff , MRSA, MERS, ... Tru-D SmartUVC ... Tru-D in action in a patient room ...
(Date:7/31/2017)... 31, 2017 Three Tru-D SmartUVC robots have arrived ... Korea . Tru-D, short for "Total Room Ultraviolet Disinfection," is a ... an environmental services (ES) professional cleans the area with traditional cleaning protocols. ... Tru-D fights germs ... "Although the BAACH has a very ...
Breaking Medicine Technology: