Abstract
The EGF receptor (EGFR) regulates important cellular processes including proliferation, differentiation, and apoptosis. EGFR is frequently overexpressed in a range of cancers and is associated with disease progression and treatment. Clinical studies have shown that EGFR mutations confer tumor sensitivity to tyrosine kinase inhibitors in patients with non–small cell lung cancer. In this study, we have conducted molecular dynamics simulations over several microseconds for wild-type and L858R mutant forms of EGFR in the ligand-free state. Close inspection of the conformations and interactions within the binding pocket reveals, converse to the wild type, that the mutant EGFR prefers to bind gefitinib, a targeted anticancer drug, rather than ATP, offering an explanation for why gefitinib is more effective in patients with EGFR mutations than those without. Mol Cancer Ther; 11(11); 2394–400. ©2012 AACR.
Footnotes
Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).
- Received June 25, 2012.
- Revision received July 20, 2012.
- Accepted July 27, 2012.
- ©2012 American Association for Cancer Research.
Volume 11, Issue 11
