Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study reveals how some molecules inhibit growth of lung cancer cells

14.03.2007
Findings provide new direction to drug design

By mapping the interlocking structures of small molecules and mutated protein "receptors" in non-small cell lung cancer (NSCLC) cells, scientists at Dana-Farber Cancer Institute and their colleagues have energized efforts to design molecules that mesh with these receptors, potentially interfering with cancer cell growth and survival.

In a study published in the March issue of Cancer Cell, researchers led by Michael Eck, MD, PhD, of Dana-Farber used X-ray crystallography to determine the structure of two mutated forms of the epidermal growth factor receptor (EGFR) in lung cancer cells. EGFR, a protein known as a tyrosine kinase, plays a key role in relaying growth signals within cells. When mutated, it can become overactive, leading to excessive cell division and cancer.

"It turns out that in some cases, the very mutation that causes the cancer in the first place is also the cancer’s Achilles’ heel," said Eck, the paper’s senior author. "We now see that inhibitors such as gefitinib actually bind more tightly to some of the cancer-causing mutants, even though they were originally developed to block the normal receptor."

... more about:
»Cancer »EGFR »Mutant »Mutation »effective »mutated »receptor

Cai-Hong Yun, PhD, of Dana-Farber is the paper’s first author.

Mutations in the EGFR kinase domain occur in approximately 16 percent of NSCLCs, but at much higher frequencies in selected populations, including nonsmokers, women, and East Asian patients. Laboratory and clinical studies have shown that tyrosine kinase inhibitors are more effective against some EGFR mutations than others, although the molecular reasons for this are unclear. By developing a better understanding of the effect of the mutations on inhibitor binding at a structural level, it may be possible to develop more effective therapies.

In the current study, Eck and his colleagues analyzed the three-dimensional structures of the normal and mutated versions of EGFR bound to several different types of inhibitor molecules. They found that two inhibitors – the drug gefitinib (marketed as Iressa(R), and a compound called AEE788 – bind especially tightly to one of the mutated forms, meaning these inhibitors are potentially more effective at blocking the growth of cancer cells containing that mutation. In the case of gefitinib, it bound 20 times more tightly to the L858R mutant than to the normal, mutation-free EGFR.

The research team concluded that the particular EGFR mutation within tumor cells determines which inhibitor molecules are likely to be able to slow or stop the growth of those cells.

"Although structural divergence in the EGFR mutants may complicate efforts to treat the disease, it may also present an advantage in that it introduces the possibility of developing inhibitors that target specific mutations, which should lead to more effective treatments," said Eck, who also an associate professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. "These targeted therapies likely would be less toxic as they, in theory, would not affect the normal functioning EGFR proteins."

Bill Schaller | EurekAlert!
Further information:
http://www.dana-farber.org

Further reports about: Cancer EGFR Mutant Mutation effective mutated receptor

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

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

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>