Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Sep;23(133):356-66.
doi: 10.1183/09059180.00004614.

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

Alexis B Cortot  1 , Pasi A Jänne  2
Affiliations
Review

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

Alexis B Cortot et al. Eur Respir Rev. 2014 Sep.

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: Disclosures can be found alongside the online version of this article at err.ersjournals.com

Figures

Figure 1.
Figure 1.
Main mechanisms of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant nonsmall cell lung cancer. SCLC: small cell lung cancer; EMT: epithelial–mesenchymal transition.
Figure 2.
Figure 2.
Gefitinib dissociation constants and Michaelis–Menten constants for the wild type and mutant epidermal growth factor receptor kinases. Data from [60].
See this image and copyright information in PMC

References

    1. Shigematsu H, Gazdar AF. Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers. Int J Cancer 2006; 118: 257–262. - PubMed
    1. Weinstein IB. Cancer. Addiction to oncogenes – the Achilles heal of cancer. Science 2002; 297: 63–64. - PubMed
    1. Paez JG, Jänne PA, Lee JC, et al. . EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304: 1497–1500. - PubMed
    1. Lynch TJ, Bell DW, Sordella R, et al. . Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350: 2129–2139. - PubMed
    1. Mok TS, Wu YL, Thongprasert S, et al. . Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–957. - PubMed

MeSH terms