HOME >> BIOLOGY >> NEWS
Lung cancer-derived EGFR mutants exhibit intrinsic differences in inhibitor sensitivity

A new study sheds light on how some small-molecule tyrosine kinase inhibitors, including two that are currently being used clinically to treat cancer, interact with wild-type and mutated forms of the epidermal growth factor receptor (EGFR). The research, published in the March issue of the journal Cancer Cell, published by Cell Press, may help to guide rational use of currently available EGFR inhibitors and provides new direction for the design and development of even more potent inhibitors that are tailored to specific EGFR mutants.

Many human malignancies exhibit mutated forms of the EGFR, a tyrosine kinase that plays a critical role in signaling pathways controlling cell proliferation and survival. Although the specific mechanisms are unclear, studies have shown that some EGFR mutations are associated with increased sensitivity to small-molecule tyrosine kinase inhibitors. To better understand how distinct mutant EGFRs interact with inhibitors on a structural level, Dr. Michael J. Eck from Harvard Medical School and the Dana-Farber Cancer Institute and colleagues studied the enzyme activity of two lung cancer-derived EGFR mutants and determined their crystal structures when bound to several different commonly used inhibitors.

The researchers found that the L858R and G719S EGFR mutants disrupt inhibitory interactions within the EGFR, leading to a characteristic overactivation of the enzyme. Structural examination of the inhibitor complexes, which included the drug gefitinib (Iressa), revealed that the mutations can affect the way the inhibitors interact with the enzyme. Interestingly, the inhibitors gefitinib and AEE788 bind much more tightly to the L858R mutant than to the wild-type EGFR. This finding explains the observation that tumors bearing this mutation have been found to be more responsive to treatment with gefitinib.

The researchers conclude that mutations of the EGFR dramatically influence inhibitor binding and suggest th
'"/>

Contact: Erin Doonan
edoonan@cell.com
617-397-2802
Cell Press
12-Mar-2007


Page: 1 2

Related biology news :

1. When two mutants collide: How XPD disorders can be partially rescued in compound heterozygotes
2. WPI professor to represent American Mathematical Society at exhibition on science funding
3. Widely used iron nanoparticles exhibit toxic effects on neuronal cells
4. Explore frontiers of science at June 7 congressional exhibition
5. Art of Science exhibit opens at Princeton
6. Robot exhibition to highlight WTEC international study of robotics
7. Gladstone Institutes assists with Exploratorium stem cell exhibit
8. The wonders of science on display at June 21 congressional exhibition
9. Institute for OneWorld Health to exhibit at BIO
10. Study finds gender differences in renal and other genes contributing to blood pressure
11. Sugar and spice and everything nice: Health differences in newborn girls and boys

Post Your Comments:
(Date:11/21/2014)... 18, 2014 According to a ... Systems (Video, RFID, Access Control, Intrusion Detection, Parking Management, ... Government), Component Service Geography - Global Forecasts to 2020", ... projected to be around $25 Billion in 2014 and ... at a CAGR of 8.69%. Browse 116 ...
(Date:11/21/2014)... -- Earlier this year Donald Spector , Chairman of ... the most prolific inventors in the world, got a ... to third party agencies. Spector envisioned this technology even ... earliest known patents in this area. Now major technology ... care, elder care and hospital applications. This technology has ...
(Date:11/21/2014)... Calif. , Nov. 20, 2014 Strict ... driver efficiency are piloting the North American and European ... of accidents growing, gesture recognition systems that are intuitive ... a mark in the industry. New ... Automotive Gesture Recognition Market in Europe ...
Breaking Biology News(10 mins):Industrial Security Systems Market Worth $38 Billion by 2020 2Industrial Security Systems Market Worth $38 Billion by 2020 3Patented Biosensor Wearable Technology Provides a More Civilized Method of Quarantine 2Patented Biosensor Wearable Technology Provides a More Civilized Method of Quarantine 3Patented Biosensor Wearable Technology Provides a More Civilized Method of Quarantine 4Gesture Recognition Intensifies with the Rise of In-car Smartphone Integration, Says Frost & Sullivan 2Gesture Recognition Intensifies with the Rise of In-car Smartphone Integration, Says Frost & Sullivan 3Gesture Recognition Intensifies with the Rise of In-car Smartphone Integration, Says Frost & Sullivan 4
(Date:11/27/2014)... DUBLIN , Nov. 27, 2014 ... of the "Global Palmitic Acid Industry Report 2014" ... http://photos.prnewswire.com/prnh/20130307/600769 The Global Palmitic Acid ... on the current state of the global palmitic acid ... of the industry including definitions, classifications, applications and industry ...
(Date:11/27/2014)... Ottawa, Ontario (PRWEB) November 27, 2014 ... Korean Ministry of Food and Drug Safety (MFDS) regulatory ... The system provides genetic results in less than 60 ... system is indicated as an aid for doctors to ... 2C19 genetic pathway. These include some of the world’s ...
(Date:11/27/2014)... OXFORD, England , November 27, 2014 ... free online on ScienceDirect   Elsevier ... information products and solutions, is pleased to announce the ... Letters . The launch ... by the rapid advances at the forefront of applied ...
(Date:11/27/2014)... November 27, 2014 Calcivis, ... management of tooth decay, today announces that it ... Calcivis® Caries Activity Imaging System. The ... medical device and consumable combination designed to transform ... decay). It involves a unique, proprietary bioluminescence approach ...
Breaking Biology Technology:Global Palmitic Acid Industry Report 2014 2Spartan Bioscience Receives Korean Regulatory Approval for First Rapid DNA Test of Mutations Affecting Metabolism of Common Drugs 2Spartan Bioscience Receives Korean Regulatory Approval for First Rapid DNA Test of Mutations Affecting Metabolism of Common Drugs 3Elsevier Announces the Launch of a New Journal: Extreme Mechanics Letters 2Elsevier Announces the Launch of a New Journal: Extreme Mechanics Letters 3Calcivis Completes Clinical Study of Novel Caries Activity Imaging System 2Calcivis Completes Clinical Study of Novel Caries Activity Imaging System 3
Cached News: