Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors

Gazdar, A F

doi:10.1038/onc.2009.198

Cited by 991Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors

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Gazdar, A F·2009·Oncogene

DOI 10.1038/onc.2009.198PMC PMC2849651

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Abstract

The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), gefitinib and erlotinib, are reversible competitive inhibitors of the tyrosine kinase domain of EGFR that bind to its adenosine-5' triphosphate-binding site. Somatic activating mutations of the EGFR gene, increased gene copy number and certain clinical and pathological features have been associated with dramatic tumor responses and favorable clinical outcomes with these agents in patients with non-small-cell lung cancer (NSCLC). The specific types of activating mutations that confer sensitivity to EGFR TKIs are present in the tyrosine kinase (TK) domain of the EGFR gene. Exon 19 deletion mutations and the single-point substitution mutation L858R in exon 21 are the most frequent in NSCLC and are termed 'classical' mutations. The NSCLC tumors insensitive to EGFR TKIs include those driven by the KRAS and MET oncogenes. Most patients who initially respond to gefitinib and erlotinib eventually become resistant and experience progressive disease. The point mutation T790M accounts for about one half of these cases of acquired resistance. Various second-generation EGFR TKIs are currently being evaluated and may have the potential to overcome T790M-mediated resistance by virtue of their irreversible inhibition of the receptor TK domain.

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Second-generation EGFR inhibitors still cannot be used to treat patients who develop resistance mutations after first-generation EGFR inhibitors, and can also lead to resistance.
“However, second-generation EGFR inhibitors still cannot be used to treat patients who develop resistance mutations after first-generation EGFR inhibitors, and can also lead to resistance.117”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [117]
T790M causes EGFR TKI resistance.
“T790M is known to cause EGFR TKI resistance, 28”
From Examining Treatment Outcomes with Erlotinib in Patients with Advanced Non–Small Cell Lung Cancer Whose Tumors Harbor Uncommon EGFR Mutations (2016) · cites this paper as [28]

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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 · see citing works
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An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor
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 · see citing works
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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 · see citing works
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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 · see citing works
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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 · see citing works
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Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib
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Riely, G. J., Pao, W. J., Ceppa, D. P., Li, A. R., Rizvi, N. A., Venkatraman, E. S., Zakowski, M. F., Kris, M. G., Ladanyi, M., & Miller, V. A. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1846 · Cited by 730 · see citing works
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Engelman, J. A., Zejnullahu, K., Gale, C.-M., Lifshits, E., Gonzales, A. J., Shimamura, T., Zhao, F., Vincent, P. W., Naumov, G. N., Bradner, J. E., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1885 · Cited by 730 · see citing works
Bronchioloalveolar Pathologic Subtype and Smoking History Predict Sensitivity to Gefitinib in Advanced Non–Small-Cell Lung Cancer
Miller, V. A., Kris, M. G., Shah, N., Patel, J. D., Azzoli, C. G., Gomez, J. E., Krug, L. M., Pao, W. J., Rizvi, N. A., Pizzo, B., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.08.158 · Cited by 729 · see citing works
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Takano, T., Ohe, Y., Sakamoto, H., Tsuta, K., Matsuno, Y., Tateishi, U., Yamamoto, S., Nokihara, H., Yamamoto, N., Sekine, I., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.01.0793 · Cited by 691 · see citing works
Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants
Greulich, H., Chen, T.-H., Feng, W., Jänne, P. A., Alvarez, J. V., Zappaterra, M., Bulmer, S. E., Frank, D. A., Hahn, W. C., Sellers, W. R., et al. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020313 · Cited by 677 · see citing works
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Shigematsu, H., & Gazdar, A. F. (2005) · International Journal of Cancer · doi:10.1002/ijc.21496 · Cited by 658 · see citing works
Self-citation
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Kosaka, T., Yatabe, Y., Endoh, H., Yoshida, K., Hida, T., Tsuboi, M., Tada, H., Kuwano, H., & Mitsudomi, T. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0714 · Cited by 595 · see citing works
Exon 19 Deletion Mutations of Epidermal Growth Factor Receptor Are Associated with Prolonged Survival in Non–Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib
Jackman, D. M., Yeap, B. Y., Sequist, L. V., Lindeman, N., Holmes, A. J., Joshi, V. A., Bell, D. W., Huberman, M. S., Halmos, B., Rabin, M. S., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0462 · Cited by 584 · see citing works
Lung adenocarcinomas induced in mice by mutant EGF receptors foundin human lung cancers respondto a tyrosine kinase inhibitor orto down-regulation of the receptors
Politi, K., Zakowski, M. F., Fan, P.-D., Schonfeld, E. A., Pao, W., & Varmus, H. E. (2006) · Genes & Development · doi:10.1101/gad.1417406 · Cited by 478 · see citing works
Kinetic Analysis of Epidermal Growth Factor Receptor Somatic Mutant Proteins Shows Increased Sensitivity to the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Erlotinib
Carey, K. D., Garton, A. J., Romero, M. S., Kahler, J., Thomson, S., Ross, S., Park, F., Haley, J. D., Gibson, N., & Sliwkowski, M. X. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0453 · Cited by 445 · see citing works
Single-Molecule Detection of Epidermal Growth Factor Receptor Mutations in Plasma by Microfluidics Digital PCR in Non–Small Cell Lung Cancer Patients
Yung, T., Chan, K. C. A., Mok, T. S. K., TONG, J. H. M., To, K., & Lo, Y. M. D. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2622 · Cited by 381 · see citing works
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Yang, C.-H., Yu, C., Shih, J., Chang, Y., Hu, F., Tsai, M.-C., Chen, K., Lin, Z., Huang, C.-J., Shun, C., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.15.6695 · Cited by 235 · see citing works
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Cortés-Funes, H., Gómez, C. G., Rosell, R., Valero, P. M., Girón, C. G., Velasco, A., Izquierdo, Á., Díz, P., Camps, C., Castellanos, D., et al. (2005) · Annals of Oncology · doi:10.1093/annonc/mdi221 · Cited by 229 · see citing works
Epidermal Growth Factor–Independent Transformation of Ba/F3 Cells with Cancer-Derived Epidermal Growth Factor Receptor Mutants Induces Gefitinib-Sensitive Cell Cycle Progression
Jiang, J., Greulich, H. E., Janne, P. A., Sellers, W. R., Meyerson, M. M., & Griffin, J. D. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1829 · Cited by 188 · see citing works
Functional Analysis of Epidermal Growth Factor Receptor (EGFR) Mutations and Potential Implications for EGFR Targeted Therapy
Kancha, R. K., von Bubnoff, N., Peschel, C., & Duyster, J. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1757 · Cited by 168 · see citing works
Effect of epidermal growth factor receptor tyrosine kinase domain mutations on the outcome of patients with non-small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors
Jänne, P. A., & Johnson, B. E. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0555 · Cited by 147 · see citing works
Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs
Bianco, R., Garofalo, S., Rosa, R., Damiano, V., Gelardi, T., Daniele, G., Marciano, R., Ciardiello, F., & Tortora, G. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604269 · Cited by 135 · see citing works
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Shepherd, F. A., & Tsao, M. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2005.04.4420 · Cited by 106 · see citing works
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Gazdar, A. F., & Minna, J. D. (2008) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0080 · Cited by 87 · see citing works
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Ikeda, K., Nomori, H., Mori, T., Sasaki, J., & Kobayashi, T. (2008) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2007.10.012 · Cited by 73 · see citing works
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Wong, K. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0369 · Cited by 49 · see citing works
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Gazdar, A. F., & Minna, J. D. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020377 · Cited by 43 · see citing works
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Authors: Gazdar, A. F.
Affiliations: The University of Texas Southwestern Medical Center (US)
Corresponding author: Gazdar, A F
ORCID: Gazdar, A F
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2009-08
Volume: 28
Issue: S1
Pages: S24-S31
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/onc.2009.198
PMC: PMC2849651
OpenAlex: W2007528734
Cited by: 991
References: 48
Citations by year: 2026: 37 · 2025: 59 · 2024: 58 · 2023: 66 · 2022: 53 · 2021: 59 · 2020: 70 · 2019: 54 · 2018: 69 · 2017: 73 · 2016: 67 · 2015: 52 · 2014: 53 · 2013: 61 · 2012: 46
FWCI: 7.87
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Boehringer Ingelheim
National Cancer Institute ((P50-CA70907, P50CA070907)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords: EGFR mutation, non-small cell lung cancer, EGFR tyrosine kinase inhibitors, gefitinib, erlotinib, exon 19 deletion, L858R mutation, T790M mutation, acquired drug resistance, KRAS, MET, gene copy number
MeSH terms: Erlotinib Hydrochloride, Gefitinib, Carcinoma, Non-Small-Cell Lung, Gene Amplification, Humans, Lung Neoplasms, Proto-Oncogene Proteins, Quinazolines, Proto-Oncogene Proteins p21(ras), Treatment Outcome, Point Mutation, Sequence Deletion, Protein Structure, Tertiary, Receptors, Growth Factor, ras Proteins, Drug Resistance, Neoplasm, Proto-Oncogene Proteins c-met, Protein Kinase Inhibitors, ErbB Receptors

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Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors

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