Open Access

EGFR mutations in non‑small cell lung cancer: Classification, characteristics and resistance to third‑generation EGFR‑tyrosine kinase inhibitors (Review)

  • Authors:
    • Zhe Tian
    • Lilan Cen
    • Feng Wei
    • Jue Dong
    • Yulan Huang
    • Yi Han
    • Zhibo Wang
    • Junhua Deng
    • Yujie Jiang
  • View Affiliations

  • Published online on: June 2, 2025     https://doi.org/10.3892/ol.2025.15121
  • Article Number: 375
  • Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mutations in EGFR (mEGFRs) in non‑small cell lung cancer (NSCLC) are key factors driving tumor development and treatment response. The present article aimed to review the classification, characteristics and molecular mechanisms of resistance to third‑generation EGFR‑tyrosine kinase inhibitors (EGFR‑TKIs) associated with mEGFRs. Activating mutations (such as L858R and exon 19 deletions) are the primary markers of sensitivity to EGFR‑TKIs, while rare mutations (such as G719X and S768I) require individualized treatment strategies. Resistance mechanisms are categorized into EGFR‑dependent (such as T790M and C797S mutations) and ‑independent (bypassing signaling activation, epithelial‑mesenchymal transition, tumor microenvironment remodeling and epigenetic regulation). Third‑generation EGFR‑TKIs (such as osimertinib) markedly improve patient survival by selectively targeting the T790M mutation, but novel resistance mutations, such as C797S, limit their long‑term efficacy. Combination therapies (such as MET proto‑oncogene, receptor tyrosine kinase/EGFR dual‑target inhibitors) and fourth‑generation TKIs (such as BLU‑945) offer novel directions to overcome resistance. Future research should focus on precise subtyping, dynamic monitoring of resistance mechanisms and regulation of the immune microenvironment to advance personalized treatment for NSCLC.
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August-2025
Volume 30 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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Spandidos Publications style
Tian Z, Cen L, Wei F, Dong J, Huang Y, Han Y, Wang Z, Deng J and Jiang Y: EGFR mutations in non‑small cell lung cancer: Classification, characteristics and resistance to third‑generation EGFR‑tyrosine kinase inhibitors (Review). Oncol Lett 30: 375, 2025.
APA
Tian, Z., Cen, L., Wei, F., Dong, J., Huang, Y., Han, Y. ... Jiang, Y. (2025). EGFR mutations in non‑small cell lung cancer: Classification, characteristics and resistance to third‑generation EGFR‑tyrosine kinase inhibitors (Review). Oncology Letters, 30, 375. https://doi.org/10.3892/ol.2025.15121
MLA
Tian, Z., Cen, L., Wei, F., Dong, J., Huang, Y., Han, Y., Wang, Z., Deng, J., Jiang, Y."EGFR mutations in non‑small cell lung cancer: Classification, characteristics and resistance to third‑generation EGFR‑tyrosine kinase inhibitors (Review)". Oncology Letters 30.2 (2025): 375.
Chicago
Tian, Z., Cen, L., Wei, F., Dong, J., Huang, Y., Han, Y., Wang, Z., Deng, J., Jiang, Y."EGFR mutations in non‑small cell lung cancer: Classification, characteristics and resistance to third‑generation EGFR‑tyrosine kinase inhibitors (Review)". Oncology Letters 30, no. 2 (2025): 375. https://doi.org/10.3892/ol.2025.15121