Featured Research

from universities, journals, and other organizations

Prostate-Cancer Find Points To New Drug Target

Date:
November 7, 2002
Source:
University Of Rochester Medical Center
Summary:
Doctors have long known that the medications they use to treat prostate cancer effectively for one to two years inevitably fail, leaving patients with few treatment options as the disease progresses, killing more than 30,000 men in the United States alone every year. Now scientists have discovered that at least one such medication has a completely unexpected side effect: The compound actually turns on a molecule known to cause cancerous cells to grow. The work, which earned an award for outstanding research from the American Urological Association, is described in the November 1 issue of the journal Cancer Research.

Scientists have uncovered a cruel twist of fate in men who have advanced prostate cancer.

Doctors have long known that the medications they use to treat prostate cancer effectively for one to two years inevitably fail, leaving patients with few treatment options as the disease progresses, killing more than 30,000 men in the United States alone every year.

Now scientists have discovered that at least one such medication has a completely unexpected side effect: The compound actually turns on a molecule known to cause cancerous cells to grow. The work, which earned an award for outstanding research from the American Urological Association, is described in the November 1 issue of the journal Cancer Research.

"It's a real surprise, that the same compound that kills cancer cells also makes them grow," says Chawnshang Chang, Ph.D., corresponding author and director of the George Whipple Laboratory for Cancer Research at the University of Rochester Medical Center. "The effect of the drug reverses completely."

Treatment for men whose prostate cancer has spread to other parts of the body takes advantage of a unique characteristic that makes prostate cancer cells vulnerable: Usually they depend on testosterone for survival. When doctors slash the supply of the hormone, most of the cancer cells die.

After surgery, radiation, and other treatment options, doctors try chemical or surgical castration or hormonal therapy, which knocks out most of a man's supply of testosterone. Oftentimes, to prevent the little remaining testosterone from feeding the cancer, doctors supplement this treatment with a drug known as an anti-androgen, which blocks the molecule through which testosterone works, the androgen receptor.

But some cancer cells survive, and for reasons that doctors have not understood, after one or two years the cancer cells are no longer vulnerable to the drugs and begin growing again. Typically, doctors remove the patients from the anti-androgen, and patients improve temporarily before the cancer takes over again.

In 1998 Chang discovered the first molecular evidence of just how such drugs can actually spur prostate-cancer cells to grow under certain conditions.

Yi-Fen Lee, Ph.D., now an assistant professor in the Department of Urology, began working with Chang to see exactly how the switch takes place. Lee studied cancer cells from four men, comparing the cells from early in their disease to their cells after hormonal therapy became ineffective. The team, which included Lee, Chang, and graduate student Wen-Jye Lin, found a molecule known as MAP kinase at much higher levels in the cells that had survived hormone therapy.

Then Chang and Lee found that, in addition to cutting off testosterone by targeting a protein known as the androgen receptor, the anti-androgen also turns on MAP kinase -- a molecule which promotes cell growth and is known to play a role in diseases like breast and prostate cancer.

The finding explains at least part of the reason why drugs like hydroxyflutamide, the anti-androgen the team studied in the Cancer Research paper, suddenly switch from being effective to being ineffective. It's a surprise, the scientists say, that the compound triggers molecular signals that don't involve the androgen receptor, which has long been the main target of prostate-cancer drug treatments.

"In all of the more than 30,000 men who die of prostate cancer each year, the cancer cells have become capable of growing even when we starve the cells of testosterone," says Edward Messing, M.D., professor and chair of urology who treats hundreds of men for prostate cancer each year. "In each one of those men, there's been a fundamental change, so that the molecule we've targeted for stopping the cancer is no longer involved in the disease. It's at this point that the disease becomes a killer. Finding an additional potential target for preventing this switch is surprising and significant."

Despite the drawbacks, the scientists stress that current treatment, including hormonal therapy, is currently the best option for patients whose cancer has spread beyond the prostate gland.

"These drugs are necessary for patients who otherwise have few options," says Lee. "However, these findings do raise some concerns that should be investigated further. Perhaps these findings will help lead to a new drug target so that men with this disease can be treated more effectively."

Working on the project besides Chang, Lee, Lin, and Messing were Jiaoti Huang, Ph.D., assistant professor of pathology and laboratory medicine; Franky Chan of the Chinese University of Hong Kong; and medical oncologist George Wilding of the University of Wisconsin. The research was funded by the National Institutes of Health.


Story Source:

The above story is based on materials provided by University Of Rochester Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Rochester Medical Center. "Prostate-Cancer Find Points To New Drug Target." ScienceDaily. ScienceDaily, 7 November 2002. <www.sciencedaily.com/releases/2002/11/021107075715.htm>.
University Of Rochester Medical Center. (2002, November 7). Prostate-Cancer Find Points To New Drug Target. ScienceDaily. Retrieved September 1, 2014 from www.sciencedaily.com/releases/2002/11/021107075715.htm
University Of Rochester Medical Center. "Prostate-Cancer Find Points To New Drug Target." ScienceDaily. www.sciencedaily.com/releases/2002/11/021107075715.htm (accessed September 1, 2014).

Share This




More Health & Medicine News

Monday, September 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
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