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Science 304 (5676): 1497-1500

Copyright © 2004 by the American Association for the Advancement of Science

EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy

J. Guillermo Paez,1,2* Pasi A. Jänne,1,2* Jeffrey C. Lee,1,3* Sean Tracy,1 Heidi Greulich,1,2 Stacey Gabriel,4 Paula Herman,1 Frederic J. Kaye,5 Neal Lindeman,6 Titus J. Boggon,1,3 Katsuhiko Naoki,1 Hidefumi Sasaki,7 Yoshitaka Fujii,7 Michael J. Eck,1,3 William R. Sellers,1,2,4{dagger} Bruce E. Johnson,1,2{dagger} Matthew Meyerson1,3,4{dagger}

Abstract: Receptor tyrosine kinase genes were sequenced in non–small cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR were found in 15of 58 unselected tumors from Japan and 1 of 61 from the United States. Treatment with the EGFR kinase inhibitor gefitinib (Iressa) causes tumor regression in some patients with NSCLC, more frequently in Japan. EGFR mutations were found in additional lung cancer samples from U.S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was hypersensitive to growth inhibition by gefitinib, but not in gefitinib-insensitive tumors or cell lines. These results suggest that EGFR mutations may predict sensitivity to gefitinib.

1 Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
2 Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
3 Departments of Pathology and Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
4 The Broad Institute at MIT and Harvard, Cambridge, MA 02142, USA.
5 Genetics Branch, National Cancer Institute, National Naval Medical Center, Bethesda, MD 20889, USA.
6 Department of Pathology, Brigham and Women's Hospital, Boston MA 02115, USA.
7 Department of Surgery 2, Nagoya City University Medical School, Nagoya 467-8601, Japan.

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Note added in proof: Similar results are being reported by T. J. Lynch et al. (28).

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: William_Sellers{at}; Bruce_Johnson{at}; Matthew_Meyerson{at}

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De-Repression of PDGFR{beta} Transcription Promotes Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in Glioblastoma Patients.
D. Akhavan, A. L. Pourzia, A. A. Nourian, K. J. Williams, D. Nathanson, I. Babic, G. R. Villa, K. Tanaka, A. Nael, H. Yang, et al. (2013)
Cancer Discovery 3, 534-547
   Abstract »    Full Text »    PDF »
High-Throughput Tyrosine Kinase Activity Profiling Identifies FAK as a Candidate Therapeutic Target in Ewing Sarcoma.
B. D. Crompton, A. L. Carlton, A. R. Thorner, A. L. Christie, J. Du, M. L. Calicchio, M. N. Rivera, M. D. Fleming, N. E. Kohl, A. L. Kung, et al. (2013)
Cancer Res. 73, 2873-2883
   Abstract »    Full Text »    PDF »
ALK Inhibitor PF02341066 (Crizotinib) Increases Sensitivity to Radiation in Non-Small Cell Lung Cancer Expressing EML4-ALK.
Y. Sun, K. A. Nowak, N. G. Zaorsky, C.-L. Winchester, K. Dalal, N. J. Giacalone, N. Liu, M. Werner-Wasik, M. A. Wasik, A. P. Dicker, et al. (2013)
Mol. Cancer Ther. 12, 696-704
   Abstract »    Full Text »    PDF »
Afatinib Prolongs Survival Compared with Gefitinib in an Epidermal Growth Factor Receptor-Driven Lung Cancer Model.
T. Ninomiya, N. Takigawa, E. Ichihara, N. Ochi, T. Murakami, Y. Honda, T. Kubo, D. Minami, K. Kudo, M. Tanimoto, et al. (2013)
Mol. Cancer Ther. 12, 589-597
   Abstract »    Full Text »    PDF »
Characteristics of Lung Cancers Harboring NRAS Mutations.
K. Ohashi, L. V. Sequist, M. E. Arcila, C. M. Lovly, X. Chen, C. M. Rudin, T. Moran, D. R. Camidge, C. L. Vnencak-Jones, L. Berry, et al. (2013)
Clin. Cancer Res. 19, 2584-2591
   Abstract »    Full Text »    PDF »
ERBB Family Mutation in Breast and Lung Cancer.
H. Greulich (2013)
Am. Assoc. Cancer Res. Educ. Book 2013, 3-8
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Gene Mutations in Squamous Cell NSCLC: Insignificance of EGFR, KRAS and PIK3CA Mutations in Prediction of EGFR-TKI Treatment Efficacy.
Anticancer Res 33, 1705-1711
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Cancer/testis antigen expression as a predictor for epidermal growth factor receptor mutation and prognosis in lung adenocarcinoma.
T. Baba, H. Shiota, K. Kuroda, Y. Shigematsu, Y. Ichiki, H. Uramoto, T. Hanagiri, and F. Tanaka (2013)
Eur J Cardiothorac Surg 43, 759-764
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Improvement in the quality of molecular analysis of EGFR in non-small-cell lung cancer detected by three rounds of external quality assessment.
Z. C. Deans, N. Bilbe, B. O'Sullivan, L. P. Lazarou, D. G. de Castro, S. Parry, A. Dodson, P. Taniere, C. Clark, and R. Butler (2013)
J. Clin. Pathol. 66, 319-325
   Abstract »    Full Text »    PDF »
Cancer Pharmacogenomics: Early Promise, But Concerted Effort Needed.
H. L. McLeod (2013)
Science 339, 1563-1566
   Abstract »    Full Text »    PDF »

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