Featured Research

from universities, journals, and other organizations

Tricking resistant cancer cells into committing suicide

Date:
October 18, 2011
Source:
Children's Hospital of Eastern Ontario Research Institute
Summary:
Scientists have found a way to trick resistant cancer cells into committing suicide following oncolytic virus therapy.

Oncolytic virology uses live viruses to sense the genetic difference between a tumor and normal cell. Once the virus finds a tumor cell, it replicates inside that cell, kills it and then spreads to adjacent tumor cells to seed a therapeutic "chain reaction." As reported in the October 18 issue of Cancer Cell, Dr. David Stojdl, a scientist from the Children's Hospital of Eastern Ontario Research Institute at the University of Ottawa has found a way to trick resistant cancer cells into committing suicide following oncolytic virus therapy.

When it comes to using oncolytic viruses to fight cancer, the outcome is a consequence of a battle between the genes that the virus has and the genes that the human host has. Using a technology called RNA Interference (RNAi) Dr. Stojdl's research team was able to systematically search through the entire human genome to find genes [that when inhibited] would make the viruses up to 10,000 times more potent at killing tumor cells without harming healthy cells. "Until now, scientists in our field have been focused on engineering the genes in the oncolytic virus itself to make them work better, and that has worked well to a point. This is the first study to look at all of the genes in the human genome to determine which ones we should manipulate to help the oncolytic therapy work better," said Dr. Stojdl.

Dr. Stojdl's research team has identified a series of genes that magnify the impact of oncolytic viruses. These genes normally control the endoplasmic reticulum stress response, or unfolded protein response. In essence, when the cell environment is toxic the cells have a tough time folding proteins. "A properly folded protein doesn't expose many sticky parts on its surface. Cells don't like mangled proteins because they get sticky. If you have sticky parts they combine with other proteins to make large, toxic 'balls' of protein -- and this can kill the cell," explained Dr. Stojdl in layman terms.

"To deal with this 'sticky situation', the cell turns on a few pre-programmed rescue systems that either turbocharge the folding process or slow down the production of new proteins until the cell can catch up. If this doesn't work, the cell commits suicide to stop the damage from spreading," explained Dr. Douglas Mahoney lead author of the study and member of the Stojdl lab.

Dr. Stojdl's team has identified a way to short-circuit these rescue systems so that tumor cells go straight to suicide and healthy cells stay intact. The strategy works by applying a mild stress to the cells to force them to turn on these rescue systems. But when these cells encounter an oncolytic virus, instead of trying to fix the unfolded proteins, the cell is triggered to commit suicide.

This triggering effect also works with some common chemotherapeutics that are used in cancer clinics around the world today.

The funding partners for this research include: Terry Fox Foundation; Ottawa Regional Cancer Foundation; Angels of Hope; CHEO Foundation and Canada Foundation for Innovation.


Story Source:

The above story is based on materials provided by Children's Hospital of Eastern Ontario Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Douglas J. Mahoney, Charles Lefebvre, Kristina Allan, Jan Brun, Cina A. Sanaei, Stephen Baird, Nelson Pearce, Susanna Grφnberg, Brian Wilson, Mikael Prakesh, Ahmed Aman, Methvin Isaac, Ahmed Mamai, David Uehling, Rima Al-Awar, Theresa Falls, Tommy Alain, David F. Stojdl. Virus-Tumor Interactome Screen Reveals ER Stress Response Can Reprogram Resistant Cancers for Oncolytic Virus-Triggered Caspase-2 Cell Death. Cancer Cell, 2011; 20 (4): 443 DOI: 10.1016/j.ccr.2011.09.005

Cite This Page:

Children's Hospital of Eastern Ontario Research Institute. "Tricking resistant cancer cells into committing suicide." ScienceDaily. ScienceDaily, 18 October 2011. <www.sciencedaily.com/releases/2011/10/111018084639.htm>.
Children's Hospital of Eastern Ontario Research Institute. (2011, October 18). Tricking resistant cancer cells into committing suicide. ScienceDaily. Retrieved April 21, 2014 from www.sciencedaily.com/releases/2011/10/111018084639.htm
Children's Hospital of Eastern Ontario Research Institute. "Tricking resistant cancer cells into committing suicide." ScienceDaily. www.sciencedaily.com/releases/2011/10/111018084639.htm (accessed April 21, 2014).

Share This



More Health & Medicine News

Monday, April 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) — Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) — In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) — A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) — The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. 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