Featured Research

from universities, journals, and other organizations

Triple-negative breast cancer target for drug development identified

Date:
October 3, 2013
Source:
University of California - San Francisco
Summary:
Often deadly "triple-negative" breast cancers might be effectively treated in many cases with a drug that targets a previously unknown vulnerability in the tumors.

Luika Timmerman, PhD, showed that growth of about one-third of triple-negative breast cancers overproduce a cell-surface protein called xCT (green), which she targeted with an FDA-approved drug to slow tumor growth.
Credit: UCSF

Often deadly "triple-negative" breast cancers might be effectively treated in many cases with a drug that targets a previously unknown vulnerability in the tumors, according to a UC San Francisco researcher who described her discovery in a study published online October 3, 2013 in the journal Cancer Cell.

Related Articles


UCSF researcher Luika Timmerman, PhD, an investigator in the UCSF Helen Diller Family Comprehensive Cancer Center, found that many cell lines obtained from triple-negative breast cancer are especially dependent on cystine, one of the 20 amino acids that are the building blocks of proteins that all cells need. Timmerman used an FDA-approved drug to inhibit activity of a transporter protein that ferries cystine into triple-negative breast cancer cells, and found that it significantly inhibited their growth in culture and when the cancer cells were transplanted into mice.

Roughly one in six women with breast cancer have triple-negative breast cancer, and only about three out of four with this type survive five years or more. These tumors sometimes grow aggressively, advancing from being undetectable to becoming difficult-to-treat between regular screening mammography exams, for instance.

Drugs now are available that effectively target the estrogen and HER2 receptor proteins, which are found in many breast tumors, and these drugs spare most normal cells in the body. However, triple-negative breast cancers are difficult to treat effectively because they do not make either of these receptors. To treat patients with triple-negative breast cancer, physicians instead use older chemotherapies that produce side effects in normal tissues, thus limiting the doses that patients can receive.

Timmerman found that she could significantly slow growth of triple-negative tumors using an FDA-approved anti-inflammatory drug called sulfasalazine to block a specific cystine transporter called xCT. While sulfasalazine itself would not be appropriate for treating cancer, Timmerman said, it could serve as a "lead compound" that could be used to develop drugs that specifically target xCT on tumor cells.

"This study of human tumors in mice and of breast cancer cell lines demonstrates the potential of targeting not only this cystine transporter, but also other metabolic abnormalities in cancer," Timmerman said.

Timmerman has spent several years studying the abnormal metabolic behavior of cancer cells, which can differ substantially from the metabolism of normal cells. "Different cancers seem to acquire different metabolic abnormalities that might in some cases give them a growth or survival advantage," she said.

"One of the strengths of this study was the large number of different cell lines I was able to test. When I saw similar results in many samples, I felt I was looking at a fundamental metabolic behavior that we could exploit to specifically target triple-negative tumors that overexpress the xCT cystine transporter, a significant group of previously untargettable tumors."

Timmerman initially focused on investigating the metabolism of the amino acid glutamine among different breast cancer-derived cell lines because glutamine metabolism was long known to be perturbed in cancer. She matched genetic "microarray" data that tracks gene activity to functional differences among tumors and tumor cell lines in culture.

But she also measured amino acids and other molecules in cell culture to detect metabolic changes. When she did so, she noticed that cystine and glutamate levels are frequently correlated in triple-negative cancers. A series of experiments led to the discovery that the cystine transporter xCT was abundant and active on many triple-negative tumors and tumor cell lines. Timmerman then tested sulfasalazine on tumors grown in mice and in tumor cell lines and found that blocking xCT activity strongly retarded the growth of triple-negative tumors.

"We have identified a compelling therapeutic target commonly expressed by breast tumors of poorest prognosis, and a lead compound for rapid, effective drug development," Timmerman said.


Story Source:

The above story is based on materials provided by University of California - San Francisco. Note: Materials may be edited for content and length.


Journal Reference:

  1. Luika A. Timmerman, Thomas Holton, Mariia Yuneva, Raymond J. Louie, Mercč Padró, Anneleen Daemen, Min Hu, Denise A. Chan, Stephen P. Ethier, Laura J. van ‘t Veer, Kornelia Polyak, Frank McCormick, Joe W. Gray. Glutamine Sensitivity Analysis Identifies the xCT Antiporter as a Common Triple-Negative Breast Tumor Therapeutic Target. Cancer Cell, 2013; DOI: 10.1016/j.ccr.2013.08.020

Cite This Page:

University of California - San Francisco. "Triple-negative breast cancer target for drug development identified." ScienceDaily. ScienceDaily, 3 October 2013. <www.sciencedaily.com/releases/2013/10/131003121258.htm>.
University of California - San Francisco. (2013, October 3). Triple-negative breast cancer target for drug development identified. ScienceDaily. Retrieved December 17, 2014 from www.sciencedaily.com/releases/2013/10/131003121258.htm
University of California - San Francisco. "Triple-negative breast cancer target for drug development identified." ScienceDaily. www.sciencedaily.com/releases/2013/10/131003121258.htm (accessed December 17, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, December 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) — Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) — Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Flu Outbreak Closing Schools in Ohio

Flu Outbreak Closing Schools in Ohio

AP (Dec. 17, 2014) — A wave of flu illnesses has forced some Ohio schools to shut down over the past week. State officials confirmed one pediatric flu-related death, a 15-year-old girl in southern Ohio. (Dec. 17) Video provided by AP
Powered by NewsLook.com
Feeling Young Might Mean A Longer Life Span

Feeling Young Might Mean A Longer Life Span

Newsy (Dec. 16, 2014) — A study published in JAMA shows that people who feel younger than their chronological age might actually live longer than those who feel old. 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