Featured Research

from universities, journals, and other organizations

Scientists show how brain tumors outsmart drugs

Date:
January 22, 2010
Source:
University of California - San Diego
Summary:
Researchers have shown one way in which gliomas, a deadly type of brain tumor, can evade drugs aimed at blocking a key cell signaling protein, epidermal growth factor receptor, that is crucial for tumor growth.

Researchers at the Ludwig Institute for Cancer Research (LICR) at the University of California, San Diego School of Medicine and Moores UCSD Cancer Center have shown one way in which gliomas, a deadly type of brain tumor, can evade drugs aimed at blocking a key cell signaling protein, epidermal growth factor receptor (EGFR),that is crucial for tumor growth. In a related finding, they also proved that a particular EGFR mutation is important not only to initiate the tumor, but for its continued growth or "maintenance" as well.

The findings, which appear during the week of January 18 in an online early edition of the Proceedings of the National Academy of Sciences, provide both new insights into the behavior of gliomas as well as potential new drug targets and treatment strategies.

"The results suggest that the expression of EGFR is required for tumors to keep growing, and we've shown for the first time that there are mechanisms that the tumor is using to circumvent the need for the receptor," said Frank Furnari, PhD, associate professor of medicine at the UCSD School of Medicine and associate investigator at the San Diego branch of the LICR, adding that other cancers may use similar tactics. "We need to find out more about the signaling pathways that brain tumors use to get around targeted therapeutics, such as those directed at EGFR."

In aggressive gliomas, extra copies of the EGFR gene are produced, and half of such tumors also carry an EGFR mutation, which ramps up tumor growth and portends a poor prognosis. Clinical trials of anti-EGFR agents have been disappointing; brain tumors may respond initially, but later become resistant to the drugs. To better understand why, Furnari, Webster Cavenee, PhD, professor of medicine and director of San Diego's LICR branch, and their group wanted to find out if the mutant EGFR was needed by tumors for their continued growth.

The team -- including postdoctoral fellows Akitake Mukasa, MD, PhD, and Jill Wykosky, PhD -- created a genetic system in mice in which they could control the expression of mutated EGFR, turning it off and on with the drug tetracycline. They found that the tumors' growth would stop for a period of time when tetracycline blocked EGFR, much like what is seen in patients who respond to EGFR inhibitors. But the tumors would start to grow again, even without EGFR, meaning something else was driving tumor growth.

The researchers examined individual tumors that had sidestepped or "escaped" the need for mutant EGFR to sustain their growth. In some cases, tumors that would normally have killed mice in 20 days were stable for months with the blocked expression of mutant EGFR. The scientists used microarray technology to test for genes that had not been previously expressed in the tumors but were now overexpressed in tumors that no longer required EGFR. They finally found one, KLHDC8 which, when inhibited, halted tumor growth.

"That finding makes us think that this gene would be a reasonable target," Cavenee said. "About half of the individual tumors that didn't need mutant EGFR to grow expressed that gene and, if we silenced the gene, those tumors did not grow."

Cavenee thinks this could be a model for the behavior of other tumors. "If the tumors use the same strategy to get around receptor inhibitors, then targeting that alternate pathway plus the receptor up front should give a longer response because it's hitting the primary event plus the escape route," he said.

Now the research team is searching for other genes expressed in tumors that can escape EGFR dependence, and looking for biological pathways that might be involved.

Other contributors include: Keith L. Ligon, MD, PhD, Dana-Farber Cancer Institute, and Lynda Chin, MD, Dana-Farber and Brigham and Women's Hospital.

Funding support came from the SUMITOMO Life Social Welfare Services Foundation, The Paul Taylor American Brain Tumor Association, the National Institutes of Health, the National Foundation for Cancer Research and the Goldhirsh Foundation.


Story Source:

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


Cite This Page:

University of California - San Diego. "Scientists show how brain tumors outsmart drugs." ScienceDaily. ScienceDaily, 22 January 2010. <www.sciencedaily.com/releases/2010/01/100119172800.htm>.
University of California - San Diego. (2010, January 22). Scientists show how brain tumors outsmart drugs. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2010/01/100119172800.htm
University of California - San Diego. "Scientists show how brain tumors outsmart drugs." ScienceDaily. www.sciencedaily.com/releases/2010/01/100119172800.htm (accessed April 23, 2014).

Share This



More Health & Medicine News

Wednesday, April 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
Study Says Most Crime Not Linked To Mental Illness

Study Says Most Crime Not Linked To Mental Illness

Newsy (Apr. 22, 2014) A new study finds most crimes committed by people with mental illness are not caused by symptoms of their illness or disorder. Video provided by Newsy
Powered by NewsLook.com
Hagel Gets Preview of New High-Tech Projects

Hagel Gets Preview of New High-Tech Projects

AP (Apr. 22, 2014) Defense Secretary Chuck Hagel is given hands-on demonstrations Tuesday of some of the newest research from DARPA _ the military's Defense Advanced Research Projects Agency program. (April 22) Video provided by AP
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. 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