Cited by 11,486Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Research Studies

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Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib

Lynch, Thomas J., Bell, Daphne W., Sordella, Raffaella, Gurubhagavatula, Sarada, Okimoto, Ross A., Brannigan, Brian W., Harris, Patricia L., Haserlat, Sara M., Supko, Jeffrey G., Haluska, Frank G., Louis, David N., Christiani, David C., Settleman, Jeff, Haber, Daniel A.·2004·New England Journal of Medicine

DOI 10.1056/nejmoa040938

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Abstract

BACKGROUND: Most patients with non-small-cell lung cancer have no response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown. METHODS: We searched for mutations in the EGFR gene in primary tumors from patients with non-small-cell lung cancer who had a response to gefitinib, those who did not have a response, and those who had not been exposed to gefitinib. The functional consequences of identified mutations were evaluated after the mutant proteins were expressed in cultured cells. RESULTS: Somatic mutations were identified in the tyrosine kinase domain of the EGFR gene in eight of nine patients with gefitinib-responsive lung cancer, as compared with none of the seven patients with no response (P<0.001). Mutations were either small, in-frame deletions or amino acid substitutions clustered around the ATP-binding pocket of the tyrosine kinase domain. Similar mutations were detected in tumors from 2 of 25 patients with primary non-small-cell lung cancer who had not been exposed to gefitinib (8 percent). All mutations were heterozygous, and identical mutations were observed in multiple patients, suggesting an additive specific gain of function. In vitro, EGFR mutants demonstrated enhanced tyrosine kinase activity in response to epidermal growth factor and increased sensitivity to inhibition by gefitinib. CONCLUSIONS: A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene, which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib. These mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor. Screening for such mutations in lung cancers may identify patients who will have a response to gefitinib.

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Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
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Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368
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Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer
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Kris, M. G., Natale, R. B., Herbst, R. S., Lynch, Jr., Prager, D., Belani, C. P., Schiller, J. H., Kelly, K., Spiridonidis, H., Sandler, A., et al. (2003) · JAMA · doi:10.1001/jama.290.16.2149 · Cited by 2,517
Self-citation
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Heinrich, M. C., Corless, C. L., Demetri, G. D., Blanke, C. D., von Mehren, M., Joensuu, H., McGreevey, L. S., Chen, C.-J., den Abbeele, A. D. V., Druker, B. J., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.190 · Cited by 2,306
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Show all 31 references

Research works printed but not linked: 3

Wakeling AE, 2002, Cancer Res, 62, 5749
Frederick L, 2000, Cancer Res, 60, 1383
Li B, 2003, Cancer Res, 63, 7443

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Thatcher, N., Chang, A., Parikh, P., Rodrigues Pereira, J., Ciuleanu, T., von Pawel, J., Thongprasert, S., Tan, E. H., Pemberton, K., Archer, V., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67625-8 · Cited by 2,079
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Zappa, C., & Mousa, S. A. (2016) · Translational Lung Cancer Research · doi:10.21037/tlcr.2016.06.07 · Cited by 1,944
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Normanno, N., Luca, A. D., Bianco, C., Strizzi, L., Mancino, M., Maiello, M. R., Carotenuto, A., Feo, G. D., Caponigro, F., & Salomon, D. S. (2005) · Gene · doi:10.1016/j.gene.2005.10.018 · Cited by 2,088
Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways
Wee, P., & Wang, Z. (2017) · Cancers · doi:10.3390/cancers9050052 · Cited by 2,027
EGF–ERBB signalling: towards the systems level
Citri, A., & Yarden, Y. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1962 · Cited by 2,056
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Wu, Y.-L., Zhou, C., Hu, C.-P., Feng, J., Lu, S., Huang, Y., Li, W., Hou, M., Shi, J. H., Lee, K. Y., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70604-1 · Cited by 1,978
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Chen, Z., Brainson, C. F., Hammerman, P. S., Kim, C. F., & Wong, K. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3775 · Cited by 1,982
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Fabian, M. A., Biggs, W., Treiber, D. K., Atteridge, C. E., Azimioara, M. D., Benedetti, M. G., Carter, T. A., Ciceri, P., Edeen, P. T., Floyd, M. B., et al. (2005) · Nature Biotechnology · doi:10.1038/nbt1068 · Cited by 1,923
Clinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Who Harbor EML4-ALK
Shaw, A. T., Yeap, B. Y., Mino-Kenudson, M. A., Digumarthy, S. R., Costa, D. B., Heist, R. S., Solomon, B., Stubbs, H., Admane, S., McDermott, U., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.6993 · Cited by 1,873
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Ventura, A., Kirsch, D. G., McLaughlin, M. E., Tuveson, D. A., Grimm, J., Lintault, L., Newman, J., Reczek, E. E., Weissleder, R., & Jacks, T. (2007) · Nature · doi:10.1038/nature05541 · Cited by 1,820
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Tsao, M., Sakurada, A., Cutz, J.-C., Zhu, C., Kamel‐Reid, S., Squire, J. A., Lorimer, I. A. J., Zhang, T., Liu, G., Daneshmand, M., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050736 · Cited by 1,815
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Zhang, X., Gureasko, J., Shen, K., Cole, P. A., & Kuriyan, J. (2006) · Cell · doi:10.1016/j.cell.2006.05.013 · Cited by 1,650
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Motzer, R. J., Michaelson, M. D., Redman, B. G., Hudes, G. R., Wilding, G., Figlin, R. A., Ginsberg, M. S., Kim, S. T., Baum, C. M., DePrimo, S. E., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.2574 · Cited by 1,630
Detection of Mutations in EGFR in Circulating Lung-Cancer Cells
Maheswaran, S., Sequist, L. V., Nagrath, S., Ulkus, L., Brannigan, B., Collura, C. V., Inserra, E., Diederichs, S., Iafrate, A. J., Bell, D. W., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0800668 · Cited by 1,617
Self-citation
Biomarker Analyses and Final Overall Survival Results From a Phase III, Randomized, Open-Label, First-Line Study of Gefitinib Versus Carboplatin/Paclitaxel in Clinically Selected Patients With Advanced Non–Small-Cell Lung Cancer in Asia (IPASS)
Fukuoka, M., Wu, Y.-L., Thongprasert, S., Sunpaweravong, P., Leong, S.-S., Sriuranpong, V., Chao, T.-Y., Nakagawa, K., Chu, D.-T., Saijo, N., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.4235 · Cited by 1,581
Lung cancer in never smokers — a different disease
Sun, S., Schiller, J. H., & Gazdar, A. F. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2190 · Cited by 1,601
Breast Cancer, Version 4.2017, NCCN Clinical Practice Guidelines in Oncology
Gradishar, W. J., Anderson, B. O., Balassanian, R., Blair, S. L., Burstein, H. J., Cyr, A. E., ELIAS, A. D., Farrar, W. B., Forero, A., Giordano, S. H., et al. (2018) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2018.0012 · Cited by 1,612
Gefitinib-Sensitizing EGFR Mutations in Lung Cancer Activate Anti-Apoptotic Pathways
Sordella, R., Bell, D. W., Haber, D. A., & Settleman, J. E. (2004) · Science · doi:10.1126/science.1101637 · Cited by 1,605
Self-citation
MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib
Bean, J., Brennan, C., Shih, J.-Y., Riely, G., Viale, A., Wang, L., Chitale, D., Motoi, N., Szoke, J., Broderick, S., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710370104 · Cited by 1,598
Double-stranded DNA in exosomes: a novel biomarker in cancer detection
Thakur, B. K., Zhang, H., Becker, A., Matei, I. R., Huang, Y., Costa‐Silva, B., Zheng, Y., Hoshino, A., Brazier, H., Xiang, J., et al. (2014) · Cell Research · doi:10.1038/cr.2014.44 · Cited by 1,629
Renal-Cell Carcinoma
Cohen, H. T., & McGovern, F. J. (2005) · New England Journal of Medicine · doi:10.1056/nejmra043172 · Cited by 1,591
The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015
Nicholson, A. G., Tsao, M., Beasley, M. B., Borczuk, A., Brambilla, E. M., Cooper, W. A., Đačić, S., Jain, D., Kerr, K. M., Lantuéjoul, S., et al. (2021) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2021.11.003 · Cited by 1,656
ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers
Bergethon, K., Shaw, A. T., Ignatius Ou, S.-H., Katayama, R., Lovly, C. M., McDonald, N. T., Massion, P. P., Siwak-Tapp, C., Gonzalez, A., Fang, R., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.35.6345 · Cited by 1,555
Epidermal Growth Factor Receptor Gene and Protein and Gefitinib Sensitivity in Non–Small-Cell Lung Cancer
Cappuzzo, F., Hirsch, F. R., Rossi, E., Bartolini, S., Ceresoli, G. L., Bemis, L., Haney, J., Witta, S. E., Danenberg, K. D., Domenichini, I., et al. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji112 · Cited by 1,538
KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib
Pao, W. J., Wang, T. Y., Riely, G. J., Miller, V. A., Pan, Q., Ladanyi, M., Zakowski, M. F., Heelan, R. T., Kris, M. G., & VARMUS, H. E. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020017 · Cited by 1,517
TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer
Herbst, R. S., Prager, D., Hermann, R., Fehrenbacher, L., Johnson, B. E., Sandler, A., Kris, M. G., Tran, H. T., Klein, P., Li, X., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.840 · Cited by 1,490
Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin
Hoadley, K. A., Yau, C. S. F., Wolf, D. M., Cherniack, A. D., Tamborero, D., Ng, S., Leiserson, M. D. M., Niu, B., McLellan, M. D., Uzunangelov, V., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.049 · Cited by 1,537
Insulin-like growth factors and neoplasia
Pollak, M., Schernhammer, E. S., & Hankinson, S. E. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1387 · Cited by 1,477
Paul Ehrlich's magic bullet concept: 100 years of progress
Strebhardt, K., & Ullrich, A. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2394 · Cited by 1,534
Mutations in the Epidermal Growth Factor Receptor and in KRAS Are Predictive and Prognostic Indicators in Patients With Non–Small-Cell Lung Cancer Treated With Chemotherapy Alone and in Combination With Erlotinib
Eberhard, D. A., Johnson, B. E., Amler, L. C., Goddard, A. D., Heldens, S., Herbst, R. S., Ince, W. L., Janne, P. A., Januario, T., Johnson, D. H., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.02.857 · Cited by 1,453
BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models
Li, D., Ambrogio, L., Shimamura, T., Kubo, S., Takahashi, M., Chirieac, L. R., Padera, R. F., Shapiro, G. I., Baum, A., Himmelsbach, F., et al. (2008) · Oncogene · doi:10.1038/onc.2008.109 · Cited by 1,447
Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors
Mellinghoff, I. K., Wang, M. Y., Vivanco, I., Haas-Kogan, D. A., Zhu, S., Dia, E. Q., Lu, K. V., Yoshimoto, K., Huang, J. H. Y., Chute, D. J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051918 · Cited by 1,442
Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer
Peifer, M., Fernandez‐Cuesta, L., Sos, M. L., George, J., Seidel, D., Kasper, L. H., Plenker, D., Leenders, F., Sun, R., Zander, T., et al. (2012) · Nature Genetics · doi:10.1038/ng.2396 · Cited by 1,404
Tyrosine Kinases as Targets for Cancer Therapy
Krause, D. S., & Etten, R. A. V. (2005) · New England Journal of Medicine · doi:10.1056/nejmra044389 · Cited by 1,402
The Concept of Synthetic Lethality in the Context of Anticancer Therapy
Kaelin, W. G. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1691 · Cited by 1,405
Extracellular vesicles as tools and targets in therapy for diseases
Kumar, M. A., Baba, S. K., Sadida, H. Q., Al-Marzooqi, S. K., Jerobin, J., Altemani, F. H., Algehainy, N. A., Alanazi, M. A., Abou‐Samra, A., Kumar, R., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01735-1 · Cited by 1,545
The ErbB/HER family of protein-tyrosine kinases and cancer
Roskoski, R. J. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.11.002 · Cited by 1,408
Lessons from the Cancer Genome
Garraway, L. A., & Lander, E. S. (2013) · Cell · doi:10.1016/j.cell.2013.03.002 · Cited by 1,377
Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology
Lindeman, N. I., Cagle, P. T., Beasley, M. B., Chitale, D. A., Dacic, S., Giaccone, G., Jenkins, R. B., Kwiatkowski, D. J., Saldivar, J.-S., Squire, J., et al. (2013) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318290868f · Cited by 1,280
Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial
Kim, E. S., Hirsh, V., Mok, T. S. K., Socinski, M. A., Gervais, R., Wu, Y.-L. L. C., Li, L.-Y., Watkins, C. L., Sellers, M. V., Lowe, E., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61758-4 · Cited by 1,241
The impact of O2 availability on human cancer
Bertout, J. A., Patel, S. A., & Simon, M. C. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2540 · Cited by 1,365
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Motzer, R. J., Rini, B. I., Bukowski, R. M., Curti, B. D., George, D. J., Hudes, G. R., Redman, B. G., Margolin, K. A., Merchan, J. R., Wilding, G., et al. (2006) · JAMA · doi:10.1001/jama.295.21.2516 · Cited by 1,226
Mutations of the Epidermal Growth Factor Receptor Gene in Lung Cancer
Kosaka, T., Yatabe, Y., Endoh, H., Kuwano, H., Takahashi, T., & Mitsudomi, T. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-2818 · Cited by 1,220
Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer
Zhang, Z., Lee, J. C., Lin, L., Olivas, V., Au, V., LaFramboise, T., Abdel-Rahman, M., Wang, X., Levine, A. D., Rho, J. K., et al. (2012) · Nature Genetics · doi:10.1038/ng.2330 · Cited by 1,224
Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial
Wu, Y.-L., Cheng, Y., Zhou, X., Lee, K. H., Nakagawa, K., Niho, S., Tsuji, F., Linke, R., Rosell, R., Corral, J., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30608-3 · Cited by 1,216
Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial
Park, K., Tan, E.-H., O'Byrne, K., Zhang, L., Boyer, M., Mok, T., Hirsh, V., Yang, J. C.-H., Lee, K. H., Lu, S., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30033-x · Cited by 1,183
Structures of Lung Cancer-Derived EGFR Mutants and Inhibitor Complexes: Mechanism of Activation and Insights into Differential Inhibitor Sensitivity
Yun, C.-H., Boggon, T. J., Li, Y., Woo, M. S., Greulich, H., Meyerson, M., & Eck, M. J. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.12.017 · Cited by 1,192
An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance
Byers, L. A., Diao, L., Wang, J., Saintigny, P., Girard, L., Peyton, M., Shen, L., Fan, Y., Giri, U., Tumula, P. K., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1558 · Cited by 1,059
Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers
Govindan, R., Ding, L., Griffith, M., Subramanian, J., Dees, N. D., Kanchi, K., Maher, C. A., Fulton, R. S., Fulton, L., Wallis, J. W., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.024 · Cited by 1,161
Nanotechnology applications in cancer
Nie, S., Xing, Y., Kim, G. J., & Simons, J. W. (2007) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.9.060906.152025 · Cited by 952

Authors: Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., Louis, D. N., Christiani, D. C., Settleman, J., & Haber, D. A.
Affiliations: Harvard University (US)
ORCID: Lynch, Thomas J.
Bell, Daphne W.
Sordella, Raffaella
Okimoto, Ross A.
Supko, Jeffrey G.
Louis, David N.
Christiani, David C.
Haber, Daniel A.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2004-05-20
Volume: 350
Issue: 21
Pages: 2129-2139
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa040938
OpenAlex: W2043696829
Cited by: 11,486
References: 31
Citations by year: 2026: 194 · 2025: 220 · 2024: 236 · 2023: 380 · 2022: 328 · 2021: 374 · 2020: 421 · 2019: 388 · 2018: 490 · 2017: 561 · 2016: 616 · 2015: 673 · 2014: 679 · 2013: 691 · 2012: 683
FWCI: 606.47
Type: journal article
Language: en
Open access: closed
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders: U.S. Public Health Service (P01 95281)
National Cancer Institute (P30-CA0516, R01CA092824, P50CA090578)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords: non-small cell lung cancer, epidermal growth factor receptor, gefitinib, EGFR mutation, tyrosine kinase inhibitors, drug sensitivity, ATP binding site, gain-of-function mutations, tyrosine kinase activity, predictive biomarkers, targeted therapy
MeSH terms: Gefitinib, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Antineoplastic Agents, Base Sequence, Carcinoma, Non-Small-Cell Lung, DNA Mutational Analysis, Epidermal Growth Factor, Female, Heterozygote, Humans, Lung Neoplasms, Male, Middle Aged, Molecular Sequence Data, Mutation, Protein-Tyrosine Kinases, Quinazolines, Sequence Deletion, Genes, erbB-1, Drug Resistance, Neoplasm, ErbB Receptors

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Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib

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