Cancer Res Treat.  2020 Oct;52(4):1288-1290. 10.4143/crt.2020.278.

EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation

• Park S
• Ku BM
• Jung HA
• Sun JM
• Ahn JS
• Lee SH
• Park K
• Ahn MJ

• KMID: 2507954
• DOI: http://doi.org/10.4143/crt.2020.278

Abstract

The non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutation eventually acquires resistant to either first or second-generation EGFR tyrosine kinase inhibitor (TKI). As the following option, targeting EGFR T790M with third-generation EGFR TKI is now established as a standard treatment option. In this study, we are reporting the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.

Keyword

Non-small cell lung cancer; Lazertinib; Third-generation EGFR tyrosine kinase inhibitor; ErbB receptors

Figure

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  Fig. 1. (A) Target sequencing in samples from lazertinib-resistant malignant ascites. Integrative genomic viewer of sample showing additional epidermal growth factor receptor (EGFR) C797S cis mutation. (B) Western blot of patient-derived cell line (PDC) samples. (C) Cell viability analyses conducted in samples after exposure to tyrosine kinase inhibitor for 72 hours. SNV, single nucleotide variant; INDEL, insertion/deletion; EpCAM, epithelial cell adhesion molecule.

Reference

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