Featured Research

from universities, journals, and other organizations

New pathway, enhancing tamoxifen to tame aggressive breast cancer identified

Date:
April 23, 2013
Source:
University of Rochester Medical Center
Summary:
Tamoxifen is a time-honored breast cancer drug used to treat millions of women with early-stage and less-aggressive disease, and now medical researchers have shown how to exploit tamoxifen's secondary activities so that it might work on more aggressive breast cancer.

Tamoxifen is a time-honored breast cancer drug used to treat millions of women with early-stage and less-aggressive disease, and now a University of Rochester Medical Center team has shown how to exploit tamoxifen's secondary activities so that it might work on more aggressive breast cancer.

The research, published in the journal EMBO Molecular Medicine, is a promising development for women with basal-like breast cancer, sometimes known as triple-negative disease. This subtype has a poor prognosis because it is notoriously resistant to treatment. In fact, basal-like cancers lack the three most common breast cancer biomarkers -- the estrogen receptor, the progesterone receptor, and theHer2/neu receptor -- and without these receptors, the usual front-line treatments are not effective.

Until recently, tamoxifen was known primarily for its ability to block estrogen receptors on the outside of cancer cells. However, new studies have suggested that when tamoxifen is given in higher doses, it works through a second mechanism of action independent of the estrogen receptor. This second mechanism was the focus of the Rochester laboratory.

Led by doctoral student Hsing-Yu Chen and Mark Noble, Ph.D., professor of Biomedical Genetics at URMC, the team studied the molecular mechanism that allows basal-like breast cancer cells to escape the secondary effects of tamoxifen, and discovered that two proteins are critical in this escape. One protein, called c-Cbl, controls the levels of multiple receptors that are critical for cancer cell function. A second protein, Cdc42, can inhibit c-Cbl and is responsible for the tumor's underlying resistance.

The team also discovered that targeting Cdc42 -- and thus inhibiting the inhibitor -- with an experimental drug compound known as ML141 restored c-Cbl's normal function. Through additional work in animal models and in human cell cultures, the team demonstrated that when ML141 is paired with tamoxifen, it enhances the ability of tamoxifen to induce cancer cell death and suppress the growth of new cancer cells. Neither drug alone had the same effect on basal-like breast cells.

Noble believes there is considerable value to targeting Cdc42, because elevated levels of the protein have been observed in multiple types of cancer. (In this context, scientists are also studying the potential for tamoxifen as a therapy for other cancers.)

The powerful ML141-tamoxifen drug combination looks like it has two more important features: It selectively targets cancer cells while sparing normal, healthy cells; and it appears to cripple cancer stem cells, the primitive cells responsible for initiating new tumors and for fueling the bulk of the tumor cell population.

"Our work is very exciting because our approach simultaneously addresses two of the most critical challenges in cancer research -- to increase the utility of existing therapies and to discover new vulnerabilities of cancer cells," said Noble, who also is a leader at UR's Stem Cell and Regenerative Medicine Institute. "Based on these discoveries, we are already pushing forward with new compounds and with new approaches that might make clinical translation of this discovery much more rapid than would occur with traditional drug-discovery approaches."

The National Institutes of Health, Susan G. Komen for the Cure, the U.S. Department of Defense, and the New York State NYSTEM initiative funded the research. Co-authors include Yin Miranda Yang, Ph.D., and Brett Stevens, Ph.D.

Hsing-Yu Chen won a Howard Hughes Medical Institute Award of Excellence in 2012 for a poster presentation on this topic.


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.


Journal Reference:

  1. Hsing-Yu Chen, Yin M. Yang, Brett M. Stevens, Mark Noble. Inhibition of redox/Fyn/c-Cbl pathway function by Cdc42 controls tumour initiation capacity and tamoxifen sensitivity in basal-like breast cancer cells. EMBO Molecular Medicine, 2013; DOI: 10.1002/emmm.201202140

Cite This Page:

University of Rochester Medical Center. "New pathway, enhancing tamoxifen to tame aggressive breast cancer identified." ScienceDaily. ScienceDaily, 23 April 2013. <www.sciencedaily.com/releases/2013/04/130423135712.htm>.
University of Rochester Medical Center. (2013, April 23). New pathway, enhancing tamoxifen to tame aggressive breast cancer identified. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2013/04/130423135712.htm
University of Rochester Medical Center. "New pathway, enhancing tamoxifen to tame aggressive breast cancer identified." ScienceDaily. www.sciencedaily.com/releases/2013/04/130423135712.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
China's Ageing Millions Look Forward to Bleak Future

China's Ageing Millions Look Forward to Bleak Future

AFP (July 24, 2014) China's elderly population is expanding so quickly that children struggle to look after them, pushing them to do something unexpected in Chinese society- move their parents into a nursing home. Duration: 02:07 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