EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib.
William Pao, Vincent Miller, Maureen Zakowski, Jennifer Doherty, Katerina Politi, Inderpal Sarkaria, Bhuvanesh Singh, Robert Heelan, Valerie Rusch, Lucinda Fulton, Elaine Mardis, Doris Kupfer, Richard ...
(Program in Cancer Biology and Genetics and Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. paow@mskcc.org)
Proc. Natl. Acad. Sci. U.S.A.
wild-type screened show_that gefitinib-refractory were containing exon_deletion point phosphotyrosine drug found cancers former egfr occur_frequently tyrosine_kinase because five concentrations phosphorylation data an related non-small_cell resected collectively_these distinct_subset gefitinib sequencing compared gene lifetime_never as_opposed levels from adenocarcinomas demonstrated tk_domain we that contrast 10-fold_lower with constructs cells whereas target occur diminished codon factor_receptor sensitive induced eight tumors analogous immunoblotting erlotinib-refractory similar most frequently mutation-positive egfr_tk 2-28 lysates was in various associated lung patients and of transiently_transfected tyrosine cigarettes reportedly who_smoked domain is which alterations gefitinib-sensitive comprise point_mutations kinase_inhibitor clinically_relevant mutations untreated current_smokers inhibited for at the smokers exon somatic_mutations within egfr_exons are types epidermal_growth undocumented seven no gefitinib_iressa erlotinib in-frame_deletions erlotinib_tarceva protein never_smokers none mutant to sensitivity or
Erlotinib in previously treated non-small-cell lung cancer.
Frances A Shepherd, José Rodrigues Pereira, Tudor Ciuleanu, Eng Huat Tan, Vera Hirsh, Sumitra Thongprasert, Daniel Campos, Savitree Maoleekoonpiroj, Michael Smylie, Renato Martins, Maximiliano van Koo ...
(Department of Medical Oncology, University Health Network, Princess Margaret Hospital Site, University of Toronto, Canada.)
N. Engl. J. Med.
group we_conducted cancer survival iv they mg_daily double-blind_trial eligible_if placebo_group one from therapy receive for stratification stratified_according was in at the were failure number who_underwent prior_platinum-based months two performance_status toxic_effects second-line_chemotherapy patients with regimens of prolongs_survival and after dose response_rate inhibitor overall_survival randomly_assigned adjusted determine_whether chemotherapy received platinum-based_chemotherapy response prior center epidermal_growth factor_receptor randomized_placebo-controlled ratio first-line median_duration stage_iiib five because can_prolong placebo erlotinib chemotherapy_regimens median_age randomization respectively categories years percent less_than favor to hazard_ratio oral or progression-free_survival non-small-cell_lung discontinued had
EGFR mutation and resistance of non-small-cell lung cancer to gefitinib.
Susumu Kobayashi, Titus J Boggon, Tajhal Dayaram, Pasi A Jänne, Olivier Kocher, Matthew Meyerson, Bruce E Johnson, Michael J Eck, Daniel G Tenen, Balázs Halmos
(Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.)
N. Engl. J. Med.
report dramatic_responses gefitinib threonine-to-methionine showed his cancer patient mutations have_been structural gene relapse led who presence from in at the change that unknown lung anilinoquinazoline two case point_mutation patients with ultimately of and identified after dna studies gefitinib-responsive resulting resistance egfr complete_remission position drug_resistance advanced_non-small-cell specimens response epidermal_growth factor_receptor mutation revealed biochemical who_had amino_acid here_we inhibitors such have mechanism is most this tumor years second during to despite sequence biopsy_specimen egfr-mutant treatment non-small-cell_lung modeling