Featured Research

from universities, journals, and other organizations

Lethal brain tumor's strength may be a weakness as well

Date:
August 16, 2010
Source:
University of California - San Diego
Summary:
Malignant gliomas are the most common subtype of primary brain tumor – and one of the deadliest. Even as doctors make steady progress treating other types of solid tumor cancers, from breast to prostate, the most aggressive form of malignant glioma, called a glioblastoma multiforme or GBM, has steadfastly defied advances in neurosurgery, radiation therapy and various conventional or novel drugs. But scientists have discovered a new signaling pathway between GBM cells – one that, if ultimately blocked or disrupted, could significantly slow or reduce tumor growth and malignancy.

Malignant gliomas are the most common subtype of primary brain tumor -- and one of the deadliest. Even as doctors make steady progress treating other types of solid tumor cancers, from breast to prostate, the most aggressive form of malignant glioma, called a glioblastoma multiforme or GBM, has steadfastly defied advances in neurosurgery, radiation therapy and various conventional or novel drugs.

But an international team of scientists, headed by researchers at the Ludwig Institute for Cancer Research (LICR) at the University of California, San Diego School of Medicine, reports in the August 15 issue of Genes & Development that they have discovered a new signaling pathway between GBM cells -- one that, if ultimately blocked or disrupted, could significantly slow or reduce tumor growth and malignancy.

More than other types of cancer, GBMs are diverse assemblages of cell subtypes featuring great genetic variation. Anti-cancer therapies that target a specific mutation or cellular pathway tend to be less effective against such tumor heterogeneity.

"These myriad genetic alterations may be one of the primary reasons why GBMs are so lethal," said Frank Furnari, PhD, associate professor of medicine at the UCSD School of Medicine and an associate investigator at the San Diego branch of the LICR.

Even with maximum treatment effort, the median patient survival rate for a diagnosed GBM is nine to 12 months -- a statistic that has not changed substantially in decades.

However, Furnari, along with postdoctoral fellows Maria-del-Mar Inda and Rudy Bonavia, and Webster Cavenee, PhD, professor of medicine and director of the San Diego LICR branch, and others noted that in GBMs only a minority of tumor cells possess a mutant form of the epidermal growth factor receptor (EGFR) gene. These cells drive the tumor's rapid, deadly growth. "Most GBM tumor cells express wild-type or normal EGFR," said Furnari. "Yet when expressed by itself, wild-type EGFR is a poor oncogene."

The scientists discovered that tumor cells with mutant EGFR secrete molecules that cause neighboring cells with wild-type EGFR to accelerate their tumorigenic growth. "The mutant cells are instructing other less malignant tumor cells to become more malignant," said Furnari.

This signaling pathway between GBM tumor cells was not known and presents a new and potentially promising chink in the armor of glioblastomas. "If we can inhibit or block this cellular communication, the tumor does not grow as quickly and may be more treatable," Furnari said. Researchers have already identified two molecules that appear to trigger EGFR activity on non-mutant tumor cells.

The findings may also provide clues in the bigger picture of how GBMs and other cancers survive and thrive. "There are other types of mutations and growth factor receptors in tumors," Furnari said. "We need to look at how they communicate. Historically, brain tumor research has focused upon the most abundantly expressed mutations, but this research suggests minority mutations play very important roles as well."

The researchers' next step will be to create a mouse model with mixed cell glioblastoma that can be used to test different therapeutics, inhibitors and blocking agents.

Co-authors of the study include Akitake Mukasa, LICR and Department of Neurosurgery, University of Tokyo; Yoshitaka Narita, LICR and Neurosurgery Division, National Cancer Center Hospital, Tokyo; Dinah W.Y. Sah, Alnylam Pharmaceuticals; Scott Vandenberg, UCSD Department of Pathology,; Cameron Brennan, Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center; Terrance G. Johns, Monash Institute of Medical Research, Monash University; Robert Bachoo, Department of Neurology, University of Texas Southwestern Medical Center; Philipp Hadwiger and Pamela Tan, both at Alnylam Europe AG; and Ronald A. DePinho, Department of Medical Oncology, Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute and Harvard Medical School.


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. "Lethal brain tumor's strength may be a weakness as well." ScienceDaily. ScienceDaily, 16 August 2010. <www.sciencedaily.com/releases/2010/08/100815111452.htm>.
University of California - San Diego. (2010, August 16). Lethal brain tumor's strength may be a weakness as well. ScienceDaily. Retrieved August 19, 2014 from www.sciencedaily.com/releases/2010/08/100815111452.htm
University of California - San Diego. "Lethal brain tumor's strength may be a weakness as well." ScienceDaily. www.sciencedaily.com/releases/2010/08/100815111452.htm (accessed August 19, 2014).

Share This




More Health & Medicine News

Tuesday, August 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
Powered by NewsLook.com
101-Year-Old Working Man Has All The Advice You Need

101-Year-Old Working Man Has All The Advice You Need

Newsy (Aug. 19, 2014) Herman Goldman has worked at the same lighting store for almost 75 years. Find out his secrets to a happy, productive life. Video provided by Newsy
Powered by NewsLook.com
Researcher Testing on-Field Concussion Scanners

Researcher Testing on-Field Concussion Scanners

AP (Aug. 19, 2014) Four Texas high school football programs are trying out an experimental system designed to diagnose concussions on the field. The technology is in response to growing concern over head trauma in America's most watched sport. (Aug. 19) Video provided by AP
Powered by NewsLook.com
American Ebola Patient Apparently Improving, Outbreak Is Not

American Ebola Patient Apparently Improving, Outbreak Is Not

Newsy (Aug. 19, 2014) Nancy Writebol, an American missionary who contracted Ebola, is apparently getting better, according to her husband. The outbreak, however, is not. 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