ArticleCancer science2018
Exploration of resistance mechanisms for epidermal growth factor receptor-tyrosine kinase inhibitors based on plasma analysis by digital polymerase chain reaction and next-generation sequencing.
Article in Cancer science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 3 of them syntheses 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
22 citing papers in PubMed, 3 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Diagnostic accuracy of next-generation sequencing (NGS) for identifying actionable mutations in advanced non-small cell lung cancer: Systematic Review and Meta-Analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Pooled it
- Comparison of liquid-based to tissue-based biopsy analysis by targeted next generation sequencing in advanced non-small cell lung cancer: a comprehensive systematic review.Journal of cancer research and clinical oncology · 2020Pooled it
- Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis.BMC cancer · 2020Pooled it
- Predicting osimertinib-treatment outcomes through EGFR mutant-fraction monitoring in the circulating tumor DNA of EGFR T790M-positive patients with non-small cell lung cancer (WJOG8815L).Molecular oncology · 2021Trial
- Association of TP53 gain-of-function mutations with early osimertinib resistance in epidermal growth factor receptor-mutant lung adenocarcinoma.ESMO open · 2026Article
- Clinical features and outcomes of first-line EGFR-TKI treatment in younger and older patients with EGFR-mutated NSCLC.Future oncology (London, England) · 2025Article
- TP53 gain-of-function mutations promote osimertinib resistance via TNF-α-NF-κB signaling in EGFR-mutated lung cancer.NPJ precision oncology · 2024Article
- Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC?Journal of clinical medicine · 2023Review
- Circulating tumour DNA biomarkers in savolitinib-treated patients with non-small cell lung cancer harbouringTherapeutic advances in medical oncology · 2022Article
- Comparing survival and treatment response of patients with acquired T790M mutation second-line osimertinib versus sequential treatment of chemotherapy followed by osimertinib: A real-world study.Thoracic cancer · 2021Article
- The emergence of various genetic alterations mediated the Osimertinib resistance of a patient harboring heterozygous germline EGFR T790M: a case report.Annals of translational medicine · 2021Article
- Liquid biopsy is a valuable tool in the diagnosis and management of lung cancer.Journal of thoracic disease · 2020Review
- Patients with advanced non-small cell lung cancer with EGFR mutations in addition to complex mutations treated with osimertinib have a poor clinical outcome: A real-world data analysis.Oncology letters · 2020Article
- External Quality Assurance of Current Technology for the Testing of Cancer-Associated Circulating Free DNA Variants.Pathology oncology research : POR · 2020Article
- Liquid Biopsy by Next-Generation Sequencing: a Multimodality Test for Management of Cancer.Current hematologic malignancy reports · 2019Review
- Mutations in exon 8 ofOncology letters · 2019Article
- Genetic Profiling of Non-Small Cell Lung Cancer at Development of Resistance to First- or Second-Generation EGFR-TKIs by CAPP-Seq Analysis of Circulating Tumor DNA.The oncologist · 2019Article
- Prior EGFR-TKI Treatment in EGFR-Mutated NSCLC Affects the Allele Frequency Fraction of Acquired T790M and the Subsequent Efficacy of Osimertinib.Targeted oncology · 2019Article
- Predictive Power of a Radiomic Signature Based onFrontiers in oncology · 2019Article
- Update on liquid biopsy in clinical management of non-small cell lung cancer.OncoTargets and therapy · 2019Review
Corrections and comments
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Authors and funding
16 authors at 12 institutions in 1 country.
Funding
Abstract
Liquid biopsy offers a potential alternative to tissue biopsy for detection of genetic alterations in cancer, and it has been introduced into clinical practice to detect the tyrosine kinase inhibitor (TKI) resistance-conferring T790M mutation of epidermal growth factor receptor (EGFR) in patients with non-small-cell lung cancer (NSCLC). We prospectively collected tumor and plasma samples from 25 NSCLC patients who harbored activating mutations of EGFR and experienced failure of treatment with afatinib. The samples were analyzed by digital PCR (dPCR) and next-generation sequencing (NGS). T790M was detected in plasma with a respective sensitivity and specificity of 83.3% and 70.0% by dPCR and 50.0% and 70.0% by NGS relative to analysis of corresponding tumor samples. Quantitation of T790M based on the ratio of the number of T790M alleles to that of activating mutation alleles (T/A ratio) improved the specificity of plasma analysis to 100% for both dPCR and NGS without a reduction in sensitivity. Although several afatinib resistance mechanisms other than T790M-including copy number gain of NRAS or MET-were identified in tumor samples, the corresponding genetic alterations were not detected in plasma. TP53 mutations were frequently identified in plasma and tumor samples, with most such mutations also having been detected before afatinib treatment. The presence of de novo TP53 mutations was associated with reduced progression-free survival. Quantitation of T790M in plasma is thus a clinically relevant approach to determine the T790M status of tumors. In addition, genetic alterations coexisting with EGFR mutations can affect the efficacy of EGFR-TKI treatment.
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Registered trials
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