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:5/11/2015)... Calif. , May 11, 2015  Synaptics ... of human interface solutions, today announced the appointment ... President and Chief Financial Officer, reporting to ... replaces Synaptics, current Chief Financial Officer, Kathleen ... 2014. Mr. Ali brings extensive ...
(Date:5/11/2015)... -- Curemark LLC, a privately held drug research and ... III double blind, randomized, placebo-controlled clinical trial to examine ... children ages 3-8 with Autism. Previously, Curemark announced the ... clinical trial for CM-AT in children ages 3-8 with ... chymotrypsin. This new trial will help determine whether all ...
(Date:5/8/2015)... -- Synaptics Inc. (NASDAQ: SYNA ), the leading developer ... executive management team will present at the following investor events: ... Conference Date: May 18, 2015 Time: 10:40am ET ... Cowen and Company Technology, Media & Telecom ... New York Palace Hotel, New York, NY ...
Breaking Biology News(10 mins):Synaptics Appoints Wajid Ali as Senior Vice President and Chief Financial Officer 2Curemark, LLC, Launches New Phase III Trial in Expanded Population of Children with Autism 2Synaptics to Present at Upcoming Investor Conferences 2
(Date:5/27/2015)... May 27, 2015 RXi Pharmaceuticals Corporation ... on discovering and developing innovative therapies primarily in ... it has commenced a public offering of shares ... of its common stock and overallotment purchase rights ... shares of common stock, warrants and overallotment purchase ...
(Date:5/27/2015)... , May 26, 2015 Research and ... the "Global Breast Cancer Monoclonal Antibodies Market ... Globally, Roche seems to dominate the breast ... Its block buster molecule, Herceptin has been able ... was found that breast cancer cells become recalcitrant ...
(Date:5/27/2015)... 27, 2015 Expanding in a big ... Avalon Biomed Inc. recently inked a deal ... Dental Co. Ltd. , the largest endodontic distributor in ... international market for Avalon Biomed, which manufactures Grey MTA ... silicate-based dental cements that have won renown from dentists ...
(Date:5/27/2015)... , May 27, 2015  Tikcro Technologies Ltd. (OTCQB: ... March 31, 2015. Aviv Boim ... continued pre-clinical work to generate functional specific antibodies, targeting ... stage, we are encouraged by the development progress. We ... new antibodies which modulate immune checkpoints gain clinical acceptance ...
Breaking Biology Technology:RXi Pharmaceuticals Announces Proposed Public Offering of Common Stock and Warrants 2RXi Pharmaceuticals Announces Proposed Public Offering of Common Stock and Warrants 3Global Breast Cancer Monoclonal Antibodies Market Outlook 2020 2Global Breast Cancer Monoclonal Antibodies Market Outlook 2020 3Dental Manufacturer Avalon Biomed Inks Major Deal with Japanese Distributor 2Dental Manufacturer Avalon Biomed Inks Major Deal with Japanese Distributor 3Tikcro Technologies Reports First Quarter 2015 Results 2Tikcro Technologies Reports First Quarter 2015 Results 3
Cached News: