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Received Dec 19, 2017; Revised Jan 23, 2018; Accepted Feb 6, 2018
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Epidermal growth factor receptor (EGFR) T790M mutation is the most common genetic change for patients of non-small-cell lung cancer (NSCLC) harboring EGFR after resistance to first-generation EGFR tyrosine kinase inhibitor (TKI) [1]. The substitution of threonine with methionine at amino acid position 790 (T790M), which reduces the ability of ATP-competitive reversible EGFR-TKI binding to EGFR tyrosine kinase domain, results in cancer cells resistant to gefitinib and erlotinib [1]. Osimertinib (Tagrisso, AZD9291, AstraZeneca) is the only FDA approved drug for lung cancer patients harboring EGFR T790M mutation. After a median of 9.6–11.0 months’ remission with osimertinib treatment, tumors will inevitably have progress. Although a lot of studies had been done, the molecular mechanisms of resistance are not yet fully understood [2, 3].
Next-generation sequencing (NGS) is a cost-effective technology capable of screening several genes simultaneously [4]. It is commonly used nowadays for sequencing mutated tumor genes with tumor tissue or plasma to identify and classify molecular subtypes, to address the unmet need for new drug targets in its category [5]. The mechanism of resistance to osimertinib or other third-generation EGFR-TKI was extremely complicated, and the reported results of mutation sites and/or mutation rates were much different among studies. Phenotype transformation, EGFR new point mutation, pathways activation, or targets loss were the strongest possibilities. Most studies reported that C797S mutation happened in 20–30% of patients after osimertinib initiation [6, 7]. The EGFR C797S mutation conferred resistance to third-generation EGFR-TKI. C797S mutation had been identified in cis or in trans with T790M mutation in tumor specimens from patients who experienced treatment failure with third-generation EGFR-TKIs. C797S and T790M mutation in trans were sensitive to first-generation plus third-generation EGFR-TKI but in cis they would be resistant to all [8]. Therefore, to elicit the mutated driver genes after resistance to third-generation EGFR-TKI is critically important.
2. Material and Methods
Patients enrolled in the study all had histologically confirmed metastatic lung adenocarcinoma. EGFR T790M mutation was confirmed by tumor tissue or serum, which was tested by the...