Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas

Cortot, Alexis B.; Jänne, Pasi A.

doi:10.1183/09059180.00004614

Cited by 158Lung Cancer Treatments and MutationsHER2/EGFR in Cancer ResearchCancer Genomics and Diagnostics

Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas

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Cortot, Alexis B., Jänne, Pasi A.·2014·European Respiratory Review

DOI 10.1183/09059180.00004614PMC PMC9487318

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Abstract

The discovery of epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC) has allowed the identification of a subset of patients whose tumours are exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs). Despite the efficacy and superiority of EGFR TKIs over chemotherapy as first-line therapy, all patients will ultimately develop progressive disease, with a median of 9-13 months progression-free survival. A better understanding of the molecular mechanisms underlying resistance to EGFR TKIs can help design new drugs and therapeutic strategies to overcome resistance. This has been illustrated by the new generation TKIs that are effective on the T790M mutation, which is the most frequent mechanism of acquired resistance to EGFR TKIs. In this article, we will address the main molecular mechanisms of primary and acquired resistance to EGFR TKIs in EGFR-mutant NSCLC.

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Several mechanisms of primary and acquired resistance to EGFR TKIs have been reported in in vitro NSCLC models and some have also been confirmed in patients.
“Several mechanisms of primary and acquired resistance to EGFR TKIs [67, 68] have been so far reported in in vitro NSCLC models and some have also been confirmed in patients.”
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 [67]
Most patients progress after 9-12 months of EGFR TKI treatment, and multiple mechanisms of acquired resistance to first-generation EGFR TKIs have been described.
“The majority of patients will progress after 9-12 months of treatment with an EGFR TKI, and various mechanisms of acquired resistance to first-generation EGFR TKIs have been described [118].”
From Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) · cites this paper as [118]

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Authors: Cortot, A. B., & Jänne, P. A.
Affiliations: Harvard University (US)
Corresponding author: Cortot, Alexis B.
ORCID: Cortot, Alexis B.
Venue: European Respiratory Review
Publisher: European Respiratory Society (ERS)
Published: 2014-08-31
Volume: 23
Issue: 133
Pages: 356-366
ISSN: 0905-9180 (ISSN-L)
1600-0617
DOI: 10.1183/09059180.00004614
PMC: PMC9487318
OpenAlex: W1983159571
Cited by: 158
References: 88
Citations by year: 2026: 3 · 2025: 3 · 2024: 3 · 2023: 12 · 2022: 16 · 2021: 22 · 2020: 10 · 2019: 21 · 2018: 16 · 2017: 19 · 2016: 15 · 2015: 16 · 2014: 2
FWCI: 2.97
Type: journal article
Language: en
Open access: diamond
doi.org
Locations: European Respiratory Review (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
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, lung adenocarcinoma, non-small cell lung cancer, EGFR tyrosine kinase inhibitors, acquired drug resistance, primary resistance, T790M mutation, molecular mechanisms of resistance
MeSH terms: Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Phenotype, Phosphotransferases, Smoking, Drug Resistance, Neoplasm, ErbB Receptors

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Molecular mechanisms of resistance in epidermal growth factor receptor-mutant lung adenocarcinomas

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