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Cited by 9,368Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Research Studies

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

Paez, J. Guillermo, Jänne, Pasi A., Lee, Jeffrey C., Tracy, Sean, Greulich, Heidi, Gabriel, Stacey, Herman, Paula, Kaye, Frederic J. +9 more·2004·Science
DOI 10.1126/science.1099314
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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.

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Crossref · 10.1126/science.1099314

Cites

25 of 25 references verified0 citation errors · 0 not checkable

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  • Reduced sensitivity to gefitinib or erlotinib in NSCLC was linked to EGFR-specific activating mutations.

    “Afterwards, studies revealed that the reduced sensitivity to gefitinib or erlotinib in NSCLC was linked to EGFR-specific activating mutations.112–116”

    From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [113]

  • The two most common EGFR-activating mutations are small in-frame deletions in exon 19 (particularly E746-A750del) and amino acid substitution in exon 21 (L858R), which collectively account for >90% of known activating EGFR mutations.

    “The two most common EGFR-activating mutations are small in-frame deletions in exon 19 (particularly E746-A750del) and amino acid substitution in exon 21 (leucine to arginine at codon 858 (L858R)), which collectively account for >90% of known activating EGFR mutations.2 3”

    From Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016) · cites this paper as [3]

  • EGFR tyrosine kinase inhibitors are effective clinical treatments for advanced non-small cell lung cancer with EGFR mutations.

    “Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective clinical therapies for EGFR mutant advanced non small cell lung cancer (NSCLC) patients (1–4).”

    From EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors (2015) · cites this paper as [2]

  • In 2004, two groups simultaneously identified somatic mutations in the tyrosine kinase domain of EGFR in a small group of NSCLC patients responding to Gefitinib.

    “In 2004 two different groups simultaneously identified the presence of somatic mutations in the tyrosine kinase domain of the EGFR in a small group of patients with NSCLC responding to the EGFR tyrosine kinase inhibitor (TKI) Gefitinib [5, 6].”

    From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [5]

  • Common EGFR mutations Del19 and L858R are associated with sensitivity to EGFR tyrosine kinase inhibitors.

    “Fortunately, common mutations (i.e. exon 19 deletions [Del19] and L858R mutation in exon 21) are associated with sensitivity to EGFR tyrosine kinase inhibitors (TKI).3, 4”

    From Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy (2016) · cites this paper as [4]

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Authors
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., Naoki, K., Sasaki, H., Fujii, Y., Eck, M. J., Sellers, W. R., Johnson, B. E., & Meyerson, M.
Affiliations
  • Broad Institute (US)
  • Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Corresponding author
  • Paez, J. Guillermo
  • Lee, Jeffrey C.
  • Sellers, William R.
  • Johnson, Bruce E.
  • Meyerson, Matthew
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2004-06-04
Volume
304
Issue
5676
Pages
1497-1500
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.1099314
OpenAlex
W2161821474
Cited by
9,368
References
25
Citations by year
2026: 118 · 2025: 167 · 2024: 178 · 2023: 225 · 2022: 291 · 2021: 294 · 2020: 315 · 2019: 333 · 2018: 430 · 2017: 488 · 2016: 505 · 2015: 563 · 2014: 569 · 2013: 575 · 2012: 549
FWCI
513.65
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
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
EGFR mutation, non-small cell lung cancer, gefitinib, EGFR tyrosine kinase inhibitors, predictive biomarkers, treatment response, lung adenocarcinoma, somatic mutations, drug sensitivity
MeSH terms
Gefitinib, Adenocarcinoma, Amino Acid Sequence, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Enzyme Inhibitors, Female, Humans, Japan, Lung Neoplasms, Male, Molecular Sequence Data, Mutation, Phosphorylation, Protein Conformation, Quinazolines, United States, Treatment Outcome, Sequence Deletion, Protein Structure, Tertiary, Genes, erbB-1, Controlled Clinical Trials as Topic, Amino Acid Substitution, Mutation, Missense, Amino Acid Motifs, Cell Line, Tumor, ErbB Receptors

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