Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists show how brain tumors outsmart drugs

20.01.2010
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.

The Moores UCSD Cancer Center is one of the nation's 40 National Cancer Institute-designated Comprehensive Cancer Centers, combining research, clinical care and community outreach to advance the prevention, treatment and cure of cancer. For more information, visit http://health.ucsd.edu/cancer. The Ludwig Institute for Cancer Research (www.licr.org) is an international organization with branches in 10 countries.

Steve Benowitz | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>