title: Inhibition of mutant EGF receptors by gefitinib: targeting an Achilles' heel of lung cancer.
abstract: Recent reports revealed a strong correlation between the presence of somatic activating mutations in the kinase domain of the EGF receptor in some human lung cancers and a striking clinical response to the selective EGF receptor inhibitor, Gefitinib. These oncogenic receptors exhibit altered signaling properties such that they selectively activate downstream survival pathways on which tumor cells have become dependent. Thus, tumor cells are effectively killed by Gefitinib treatment. In addition, the catalytic function of the mutant receptors exhibits increased sensitivity to Gefitinib, raising the possibility that two distinct consequences of Gefitinib action account for its clinical efficacy.
authors.affiliation: Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, Department of Medicine, Harvard Medical School, Charlestown, USA. Settleman@helix.mgh.harvard.edu
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Settleman
mesh_terms: D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib