Uncommon Epidermal Growth Factor Receptor mutations in non-small cell lung cancer and their mechanisms of EGFR tyrosine kinase inhibitors sensitivity and resistance

Massarelli, Erminia; Johnson, Faye M.; Erickson, Heidi S.; Wistuba, Ignacio I.; Papadimitrakopoulou, Vassiliki

doi:10.1016/j.lungcan.2013.01.018

Cited by 111Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

Uncommon Epidermal Growth Factor Receptor mutations in non-small cell lung cancer and their mechanisms of EGFR tyrosine kinase inhibitors sensitivity and resistance

Massarelli, Erminia, Johnson, Faye M., Erickson, Heidi S., Wistuba, Ignacio I., Papadimitrakopoulou, Vassiliki·2013·Lung Cancer

DOI 10.1016/j.lungcan.2013.01.018

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Abstract

Therapy targeted against the epidermal growth factor receptor (EGFR) has demonstrated dramatic tumor responses and favorable clinical outcomes in a select group of non-small cell lung cancer (NSCLC) patients whose tumors harbor EGFR activating mutations. The best characterized of the mutations conferring sensitivity to EGFR tyrosine kinase inhibitors (TKIs) are deletions in exon 19 and a point mutation in exon 21 (L858R). Likewise, the most common mutation that confers resistance is the T790M point mutation. However several other mutations have been reported and several have been characterized as regards their role in sensitivity or resistance to EGFR TKIs. Resistance to the EGFR TKIs erlotinib and gefitinib, and the newer irreversible EGFR TKIs is a problem of fundamental importance. Recognition of the presence and significance of specific EGFR mutations is important for appropriate therapeutic implementation of EGFR TKIs and research and development of mutation-specific inhibitors. We summarize the literature and present an overview of the subject of less common EGFR mutations and their clinical significance, with an emphasis on EGFR TKI sensitivity or resistance.

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Patients with atypical EGFR mutations show heterogeneous and reduced responses to EGFR inhibitors, including osimertinib.
“Patients with atypical EGFR mutations show heterogeneous and reduced responses to EGFR inhibitors1,3,7–10, including osimertinib12.”
From Structure-based classification predicts drug response in EGFR-mutant NSCLC (2021) · cites this paper as [8]

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Mutation Spectrum of EGFR From 21,324 Chinese Patients With Non-Small Cell Lung Cancer (NSCLC) Successfully Tested by Multiple Methods in a CAP-Accredited Laboratory
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Clinical Genotyping of Non–Small Cell Lung Cancers Using Targeted Next-Generation Sequencing: Utility of Identifying Rare and Co-mutations in Oncogenic Driver Genes
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Authors: Massarelli, E., Johnson, F. M., Erickson, H. S., Wistuba, I. I., & Papadimitrakopoulou, V.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
Corresponding author: Papadimitrakopoulou, Vassiliki
ORCID: Massarelli, Erminia
Johnson, Faye M.
Wistuba, Ignacio I.
Papadimitrakopoulou, Vassiliki
Venue: Lung Cancer
Publisher: Elsevier BV
Published: 2013-06
Volume: 80
Issue: 3
Pages: 235-241
ISSN: 0169-5002 (ISSN-L)
DOI: 10.1016/j.lungcan.2013.01.018
OpenAlex: W2014993624
Cited by: 110
References: 86
Citations by year: 2026: 2 · 2025: 5 · 2024: 9 · 2023: 5 · 2022: 16 · 2021: 8 · 2020: 11 · 2019: 9 · 2018: 8 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 10 · 2013: 4
FWCI: 1.56
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Lung Cancer (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
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, drug resistance, erlotinib, gefitinib, exon 19 deletion, L858R mutation, T790M mutation, targeted therapy
MeSH terms: Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, Exons, Humans, Point Mutation, Drug Resistance, Neoplasm, Protein Kinase Inhibitors, ErbB Receptors

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Uncommon Epidermal Growth Factor Receptor mutations in non-small cell lung cancer and their mechanisms of EGFR tyrosine kinase inhibitors sensitivity and resistance

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