Featured Research

from universities, journals, and other organizations

Experimental drug reduces tumor resistance to breast cancer therapy

Date:
January 7, 2010
Source:
Georgetown University Medical Center
Summary:
Researchers have found a way to cleverly override signals that tell breast cancer cells to keep surviving in the face of anticancer treatment. The investigational agent they used renews the sensitivity of these breast cancer cells to treatment by fulvestrant which had stopped working.

Researchers at Georgetown Lombardi Comprehensive Cancer Center have found a way to cleverly override signals that tell breast cancer cells to keep surviving in the face of anticancer treatment. The investigational agent they used renews the sensitivity of these breast cancer cells to treatment by fulvestrant (Faslodex®) which had stopped working.

They add that this method will likely work equally well with tamoxifen, the world's most commonly used breast cancer drug. Both fulvestrant and tamoxifen are used in women with estrogen-receptor-positive metastatic breast cancer and both exhibit substantial issues with eventual tumor resistance. Fulvestrant is typically used when women stop responding to tamoxifen.

In the January 6, 2010 issue of PLoS ONE, the Lombardi researchers report that the agent (YC137) they tested, a broadly active drug that inhibits multiple members of the Bcl2 family of proteins, restored the ability of breast cancer cells to self destruct in a number of different ways.

This is a new finding, given that it was believed that the Bcl2 protein family is involved in just apoptosis, one method of cell death that programs self destruction, says the study's lead investigator, Robert Clarke, PhD, DSc, a professor of oncology and physiology & biophysics at Lombardi, a part of Georgetown University Medical Center (GUMC). Clarke is also the interim director of GUMC's Biomedical Graduate Research Organization.

"There are other ways that a cell dies, and our research shows that Bcl2 is involved in these processes as well. That means it is possible to hit a number of these Bcl2 pathways that breast cancer cells use to evade the killing effects of a drug," Clarke says. "We need to block all of the alternative routes cancer uses to survive."

The routes include pushing a cell into autophagy, in which a damaged cell is destroyed and digested, and necrosis, in which the cell falls apart when apoptosis and autophagy fail. Until now, it had not been known that the protein family was involved in regulating autophagy and necrosis in response to anticancer drugs like fulvestrant, Clarke says.

In this study, laboratory experiments using the investigational agent restored the ability of fulvestrant to bind to and destroy estrogen receptors in several different lines of tumor cells. Normally this destruction would signal the cell to die but Bcl2 proteins, which are highly expressed in many different kinds of cancer, can save the cell.

The findings explain why treatments that target just one member of the Bcl2 family have not done as well as anticipated in clinical trials, and it suggests that using an agent that can hit multiple Bcl2 proteins will be more effective, says Clarke.

That could mean a Bcl2 blocking drug could be administered along with other traditional cancer therapies to keep the tumor cells from becoming resistant due to activation of a Bcl2 survival mechanism.

Several Bcl2 blocking drugs are now in clinical trials, Clarke adds. In addition, other strategies to overcoming tumor resistance are being explored at Lombardi including using agents (sorafenib) that destroy mechanisms the cell creates to survive the onslaught of drugs. Also, researchers are looking at the use of estrogen to kill breast tumor cells, which represents a paradigm shift in the way we think estrogen receptor-positive breast cancer behaves. If successful, these agents could possibly be tested in patients who haven taken fulvestrant or tamoxifen and don't respond as they should, or who have become resistant to either or both drugs, he says.

But while this study has added to knowledge of how cells can be forced to self-destruct, Clarke says there may be other proteins that cancer uses to protect against cell death. "We are using a systems biology approach that looks at all genes and proteins involved in breast cancer to identify what else is playing a role in keeping these cells alive," he says. "We want to know what all the targets are that we need to hit to make sure these cells are destroyed, and these might provide other exciting opportunities for drug discovery."

The study was funded by grants from the Department of Defense Breast Cancer Research Program and from the U.S. Health and Human Services.


Story Source:

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


Journal Reference:

  1. Crawford et al. Co-Inhibition of BCL-W and BCL2 Restores Antiestrogen Sensitivity through BECN1 and Promotes an Autophagy-Associated Necrosis. PLoS ONE, 2010; 5 (1): e8604 DOI: 10.1371/journal.pone.0008604

Cite This Page:

Georgetown University Medical Center. "Experimental drug reduces tumor resistance to breast cancer therapy." ScienceDaily. ScienceDaily, 7 January 2010. <www.sciencedaily.com/releases/2010/01/100106003611.htm>.
Georgetown University Medical Center. (2010, January 7). Experimental drug reduces tumor resistance to breast cancer therapy. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2010/01/100106003611.htm
Georgetown University Medical Center. "Experimental drug reduces tumor resistance to breast cancer therapy." ScienceDaily. www.sciencedaily.com/releases/2010/01/100106003611.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) — Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Nigeria Ups Ebola Stakes on 1st Death

Nigeria Ups Ebola Stakes on 1st Death

Reuters - Business Video Online (July 29, 2014) — Nigerian authorities have shut and quarantined a Lagos hospital where a Liberian man died of the Ebola virus, the first recorded case of the highly-infectious disease in Africa's most populous economy. David Pollard reports Video provided by Reuters
Powered by NewsLook.com
Running 5 Minutes A Day Might Add Years To Your Life

Running 5 Minutes A Day Might Add Years To Your Life

Newsy (July 29, 2014) — According to a new study, just five minutes of running or jogging a day could add years to your life. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Poses Little Threat To U.S.: CDC

Ebola Outbreak Poses Little Threat To U.S.: CDC

Newsy (July 29, 2014) — The Ebola outbreak in West Africa poses little threat to Americans, according to officials with the Centers for Disease Control and Prevention. 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:
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