Featured Research

from universities, journals, and other organizations

Targeted Combination Therapy Triggers Cell Death in Mouse Models of Metastatic Cancer

Date:
April 30, 2008
Source:
Journal of the National Cancer Institute
Summary:
A combination of two targeted drugs--one that blocks protein breakdown and one that activates the programmed cell death pathway--reduces the number of tumor metastases in mouse models of kidney and breast cancer. The combination also prolonged overall survival in mice with kidney cancer. Bortezomib blocks the activity of the proteasome, an enzyme complex which degrades misfolded or unwanted proteins. Bortezomib has been approved by the U.S. Food and Drug Administration for the treatment of multiple myeloma, but its activity against solid tumors is still being tested.

A combination of two targeted drugs--one that blocks protein breakdown and one that activates the programmed cell death pathway--reduces the number of tumor metastases in mouse models of kidney and breast cancer. The combination also prolonged overall survival in mice with kidney cancer.

Bortezomib blocks the activity of the proteasome, an enzyme complex which degrades misfolded or unwanted proteins. Bortezomib has been approved by the U.S. Food and Drug Administration for the treatment of multiple myeloma, but its activity against solid tumors is still being tested.

The immune system in both humans and mice may use the TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) pathway to eliminate precancerous cells by inducing programmed cell death, or apoptosis. Antibodies that bind to the TRAIL receptor can activate the cell death pathway, as does the TRAIL ligand. The research group led by Thomas Sayers, Ph.D., of SAIC-Fredrick Inc., at the National Cancer Institute in Frederick, Md., had previously shown that bortezomib sensitizes some tumors to TRAIL-mediated cell death.

In the current study, the researchers tested whether the combination of bortezomib and an antibody that binds and stimulates the TRAIL receptor-2, called MD5-1, was more effective at killing cancer cells grown in culture than either drug alone. They also tested the combination's ability to improve the outcome of mice that had been injected intravenously with kidney and breast cancer cell lines.

Treating cancer cells with the combination of bortezomib and MD5-1 increased cell death in kidney cancer cells from 34 percent to 95 percent, compared with MD5-1 alone, and from 20 percent to 85 percent in the breast cancer cells. Mice treated with the combination showed a highly significant reduction in metastases as compared with either drug alone. Overall survival was extended in kidney cancer-bearing mice treated with the combination, with 73 percent of the mice alive at 180 days, compared with a median survival of 42 days in the mice treated with the single-agent MD5-1.

"This regimen showed no evidence of host toxicity," the authors write. "These results thus provide a rationale for the administration of bortezomib in vivo to sensitize tumor cells to the apoptotic effects of TRAIL receptor agonist antibodies or TRAIL ligand to promote solid tumor regression."

This research was reported April 29 in the Journal of the National Cancer Institute.


Story Source:

The above story is based on materials provided by Journal of the National Cancer Institute. Note: Materials may be edited for content and length.


Cite This Page:

Journal of the National Cancer Institute. "Targeted Combination Therapy Triggers Cell Death in Mouse Models of Metastatic Cancer." ScienceDaily. ScienceDaily, 30 April 2008. <www.sciencedaily.com/releases/2008/04/080429164733.htm>.
Journal of the National Cancer Institute. (2008, April 30). Targeted Combination Therapy Triggers Cell Death in Mouse Models of Metastatic Cancer. ScienceDaily. Retrieved September 21, 2014 from www.sciencedaily.com/releases/2008/04/080429164733.htm
Journal of the National Cancer Institute. "Targeted Combination Therapy Triggers Cell Death in Mouse Models of Metastatic Cancer." ScienceDaily. www.sciencedaily.com/releases/2008/04/080429164733.htm (accessed September 21, 2014).

Share This



More Health & Medicine News

Sunday, September 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. 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