ArticleOncotarget2016
Mutational profiling of non-small-cell lung cancer patients resistant to first-generation EGFR tyrosine kinase inhibitors using next generation sequencing.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Comparison of T790M Acquisition After Treatment With First- and Second-Generation Tyrosine-Kinase Inhibitors: A Systematic Review and Network Meta-Analysis.Frontiers in oncology · 2022Pooled it
- Efficacy and safety of PD-1 blockade-activated neoantigen specific cellular therapy for advanced relapsed non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2025Trial
- Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study.Targeted oncology · 2021Trial
- Efficacy of TKIs in non-small cell lung cancer with atypical EGFR p.L747P and p.L747S mutations.Frontiers in oncology · 2026Article
- TET2 repression contributes to EGFR TKI resistance in EGFR-mutant non-small cell lung cancer through regulating AXIN2 methylation.Scientific reports · 2025Article
- Landscape of TET2 Mutations: From Hematological Malignancies to Solid Tumors.Cancer medicine · 2025Review
- Case Report: Evolution and targeted therapy of an EGFR-mutant large-cell neuroendocrine carcinoma.Frontiers in oncology · 2025Article
- Association between epidermal growth factor receptor gene mutation status and short-term efficacy of first-line platinum-containing chemotherapy in advanced non-small cell lung cancer.Biomedical reports · 2022Article
- Liquid biopsy uncovers distinct patterns of DNA methylation and copy number changes in NSCLC patients with different EGFR-TKI resistant mutations.Scientific reports · 2021Article
- Unique Genomic Alterations of Cerebrospinal Fluid Cell-Free DNA Are Critical for Targeted Therapy of Non-Small Cell Lung Cancer With Leptomeningeal Metastasis.Frontiers in oncology · 2021Article
- Article
- Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC).Lung cancer (Amsterdam, Netherlands) · 2019Review
- Co-occurring genetic alterations predict distant metastasis and poor efficacy of first-line EGFR-TKIs in EGFR-mutant NSCLC.Journal of cancer research and clinical oncology · 2019Article
- Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors.The Journal of clinical investigation · 2019Article
- Loss of EGFR confers acquired resistance to AZD9291 in an EGFR-mutant non-small cell lung cancer cell line with an epithelial-mesenchymal transition phenotype.Journal of cancer research and clinical oncology · 2018Article
- Cumulative smoking dose affects the clinical outcomes of EGFR-mutated lung adenocarcinoma patients treated with EGFR-TKIs: a retrospective study.BMC cancer · 2018Article
- Non-small cell lung cancer harboring a rare EGFR L747P mutation showing intrinsic resistance to both gefitinib and osimertinib (AZD9291): A case report.Thoracic cancer · 2018Article
- Epigenetic dysregulation ofOncotarget · 2018Article
- SMAD4 and NF1 mutations as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese metastatic colorectal cancer patients.BMC cancer · 2018Article
- Comparison of cross-platform technologies for EGFR T790M testing in patients with non-small cell lung cancer.Oncotarget · 2017Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epithelial growth factor receptor (EGFR) mutations invariably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). Identification of actionable genetic alterations conferring drug-resistance can be helpful for guiding the subsequent treatment decision. One of the major resistant mechanisms is secondary EGFR-T790M mutation. Other mechanisms, such as HER2 and MET amplifications, and PIK3CA mutations, were also reported. However, the mechanisms in the remaining patients are still unknown. In this study, we performed mutational profiling in a cohort of 83 NSCLC patients with TKI-sensitizing EGFR mutations at diagnosis and acquired resistance to three different first-generation EGFR TKIs using targeted next generation sequencing (NGS) of 416 cancer-related genes. In total, we identified 322 genetic alterations with a median of 3 mutations per patient. 61% of patients still exhibit TKI-sensitizing EGFR mutations, and 36% of patients acquired EGFR-T790M. Besides other known resistance mechanisms, we identified TET2 mutations in 12% of patients. Interestingly, we also observed SOX2 amplification in EGFR-T790M negative patients, which are restricted to Icotinib treatment resistance, a drug widely used in Chinese NSCLC patients. Our study uncovered mutational profiles of NSCLC patients with first-generation EGFR TKIs resistance with potential therapeutic implications.
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