EGFR-mutated lung cancer: a paradigm of molecular oncology

Zhang, Zhenfeng; Stiegler, Amy L.; Boggon, Titus J.; Kobayashi, Susumu; Halmos, Balazs

doi:10.18632/oncotarget.186

Cited by 198Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchLung Cancer Research Studies

EGFR-mutated lung cancer: a paradigm of molecular oncology

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Zhang, Zhenfeng, Stiegler, Amy L., Boggon, Titus J., Kobayashi, Susumu, Halmos, Balazs·2010·Oncotarget

DOI 10.18632/oncotarget.186PMC PMC3001953

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Abstract

The development of EGFR tyrosine kinase inhibitors for clinical use in non-small cell lung cancer and the subsequent discovery of activating EGFR mutations have led to an explosion of knowledge in the fields of EGFR biology, targeted therapeutics and lung cancer research. EGFR-mutated adenocarcinoma of the lung has clearly emerged as a unique clinical entity necessitating the routine introduction of molecular diagnostics into our current diagnostic algorithms and leading to the evidence-based preferential usage of EGFR-targeted agents for patients with EGFR-mutant lung cancers. This review will summarize our current understanding of the functional role of activating mutations, key downstream signaling pathways and regulatory mechanisms, pivotal primary and acquired resistance mechanisms, structure-function relationships and ultimately the incorporation of molecular diagnostics and small molecule EGFR tyrosine kinase inhibitors into our current treatment paradigms.

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EGFR signaling is commonly deregulated in cancer through genetic mutations of the receptor.
“EGFR signaling is commonly deregulated in cancer through different mechanisms, including genetic mutations of the receptor [2, 3].”
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 [3]

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[29]Ji H ZX Yuza Y Shimamura T Li D Protopopov A Jung BL McNamara K Xia H Glatt KA Thomas RK Sasaki H Horner JW Eck M Mitchell A Sun Y Al-Hashem R Bronson RT Rabindran SK Discafani CM Maher E Shapiro GI Meyerson M Wong KK Epidermal growth factor receptor variant iii mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors Proc Natl Acad Sci U S A 2006 103 7817 7822 16672372 PMC1456806
[85]Zhang Z LaFramboise T Abdel-Rahman M Levine A Ma P Halmos B. H Overexpression of axl as a novel acquired resistance mechanism in egfr-mutated non-small cell lung cancer cells AACR Proceedings 2010 LB-307.
[102]Shepherd FA Rodrigues Pereira J Ciuleanu T Tan EH Hirsh V Thongprasert S Campos D Maoleekoonpiroj S Smylie M Martins R van Kooten M Dediu M Findlay B Tu D Johnston D Bezjak A Clark G Santabarbara P Seymour L Erlotinib in previously treated non-small-cell lung cancer N Engl J Med 2005 353 123 132 16014882

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Authors: Zhang, Z., Stiegler, A. L., Boggon, T. J., Kobayashi, S., & Halmos, B.
Affiliations: NewYork–Presbyterian Hospital (US)
Yale University (US)
Beth Israel Deaconess Medical Center (US)
Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, New York Presbyterian Hospital- Columbia University Medical Center, New York, NY, USA
Corresponding author: Zhang, Zhenfeng
ORCID: Zhang, Zhenfeng
Stiegler, Amy L.
Boggon, Titus J.
Kobayashi, Susumu
Venue: Oncotarget
Publisher: Impact Journals, LLC
Published: 2010-10-25
Volume: 1
Issue: 7
Pages: 497-514
ISSN: 1949-2553 (ISSN-L)
DOI: 10.18632/oncotarget.186
PMC: PMC3001953
OpenAlex: W2097152766
Cited by: 197
References: 119
Citations by year: 2026: 6 · 2025: 7 · 2024: 7 · 2023: 11 · 2022: 5 · 2021: 5 · 2020: 13 · 2019: 9 · 2018: 13 · 2017: 18 · 2016: 14 · 2015: 14 · 2014: 16 · 2013: 20 · 2012: 24
FWCI: 3.29
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
Locations: Oncotarget (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: American Cancer Society
Flight Attendant Medical Research Institute
National Institutes of Health
National Cancer Institute (T32CA009085, R00CA126026, T32CA09085)
National Institute of General Medical Sciences (R00 GM088240, R01GM088240)
National Institute of Allergy and Infectious Diseases (R01AI075133, R00 AI075133)
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-mutant lung cancer, non-small cell lung cancer, EGFR tyrosine kinase inhibitors, EGFR activating mutations, lung adenocarcinoma, molecular diagnosis, targeted therapy, acquired drug resistance, downstream signaling pathways, structure-function relationship, molecular oncology
MeSH terms: Animals, Antineoplastic Agents, Carcinoma, Humans, Lung Neoplasms, Medical Oncology, Models, Biological, Molecular Diagnostic Techniques, Protein Kinase Inhibitors, Mutant Proteins, Molecular Targeted Therapy, ErbB Receptors

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EGFR-mutated lung cancer: a paradigm of molecular oncology

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