Featured Research

from universities, journals, and other organizations

Protein that fuels lethal breast cancer growth emerges as potential new drug target

Date:
October 19, 2011
Source:
Duke University Medical Center
Summary:
A protein in the nucleus of breast cancer cells that plays a role in fueling the growth of aggressive tumors may be a good target for new drugs, reports a research team.

A protein in the nucleus of breast cancer cells that plays a role in fueling the growth of aggressive tumors may be a good target for new drugs, reports a research team at the Duke Cancer Institute.

Related Articles


The finding, published in the Oct. 18, 2011, print issue of the journal Cancer Cell, presents a potential new way to inhibit breast cancer growth among so-called estrogen receptor negative cancers, which are especially lethal because they don't respond to current hormone therapies.

"This is validation of a new drug target for a subset of breast cancers that have poor treatment options," said the study's senior author, Donald McDonnell, PhD., chairman of the Duke Department of Pharmacology and Cancer Biology.

In about 75 percent of breast cancers, the growth of tumors is driven by estrogen. Current treatments for these tumors work by blocking the effects of the hormone.

But about 25 percent of breast cancers are not fueled by estrogen. Among the most common malignancies in this category are HER2-positive tumors, where human epidermal growth factor receptor 2 is in excess on the surface of tumor cells. Treatments have been developed to disable the activity of HER2 and impede tumor growth, but the tumors often grow resistant.

McDonnell and his team focused on a protein inside the nucleus of tumor cells that has a relationship with HER2. Known as estrogen-related receptor alpha (ERRα), the protein was identified in the 1980s and misleadingly dubbed an estrogen receptor. It is not; instead, it controls genes involved in energy metabolism.

But ERRα does appear to play a role in spurring tumor growth in breast cancers. Using a genomic analysis to profile 800 breast tumors, McDonnell's team identified a correlation between the activity of the protein and the aggressiveness of estrogen-negative malignancies.

"When that ERRα receptor is active, the outcome of these patients is much, much worse," McDonnell said. "The question is why?"

The protein appears to ignite tumor growth after getting a signal from different hormone receptors. One trigger is HER2, the growth factor receptor, and another is IGF-1R, which binds to an insulin-like hormone. As a result, ERRα is active in all breast cancer tumors where either HER2 or IGF-1R is also active, a scenario that occurs most frequently in estrogen receptor negative cancers.

Using a drug candidate that is still investigational, the scientists found they could shut down ERRα in cellular models of breast cancer even without knowing everything that was causing its activation. By silencing ERRα with the experimental drug in laboratory tests, the researchers stopped the tumor cells from proliferating.

"There are a lot of proteins that play important roles in breast cancer pathogenesis, but disappointingly, the activity of only a few of these proteins can be inhibited by drugs," McDonnell said. "In contrast, it's relatively easy to interfere with ERRα's function. So instead of looking for the pathways that lead to ERRα activation, we can aim directly at the target ERRα. It doesn't matter what's upstream."

McDonnell said the new drug approach could be applied to colon, ovarian and other cancers, since ERRα is highly active in different malignancies.

"The initial excitement is we have found a target that seems to be important for estrogen-negative cancers," McDonnell said.

The research team is now investigating the reason why higher ERRα activity results in more aggressive breast cancer tumors. The researchers are also helping develop new drugs to inhibit the activity of this receptor.

In addition to McDonnell, study authors include: Ching-Yi Chang; Dmitri Kazmin; Jeff S. Jasper; Rebecca Kunder; and William J Zuercher.

The study was funded by a grant from the National Institutes of Health, and an award from The American Recovery and Reinvestment Act of 2009.

Study author Zuercher reported he is an employee and stockholder of GlaxoSmithKline.


Story Source:

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


Journal Reference:

  1. Ching-yi Chang, Dmitri Kazmin, Jeff S. Jasper, Rebecca Kunder, William J. Zuercher, Donald P. McDonnell. The Metabolic Regulator ERRα, a Downstream Target of HER2/IGF-1R, as a Therapeutic Target in Breast Cancer. Cancer Cell, 20(4) pp. 500 - 510; 18 October 2011 DOI: 10.1016/j.ccr.2011.08.023

Cite This Page:

Duke University Medical Center. "Protein that fuels lethal breast cancer growth emerges as potential new drug target." ScienceDaily. ScienceDaily, 19 October 2011. <www.sciencedaily.com/releases/2011/10/111017124243.htm>.
Duke University Medical Center. (2011, October 19). Protein that fuels lethal breast cancer growth emerges as potential new drug target. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2011/10/111017124243.htm
Duke University Medical Center. "Protein that fuels lethal breast cancer growth emerges as potential new drug target." ScienceDaily. www.sciencedaily.com/releases/2011/10/111017124243.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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