ArticleFrontiers in oncology2021
Advanced NSCLC Patients With EGFR T790M Harboring TP53 R273C or KRAS G12V Cannot Benefit From Osimertinib Based on a Clinical Multicentre Study by Tissue and Liquid Biopsy.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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13 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- Comprehensive Liquid Biopsy Approaches for the Clinical Management of Lung Cancer Using Multiple Biological Matrices.International journal of molecular sciences · 2025Review
- Article
- CRISPR-mediated ablation of TP53 and EGFR mutations enhances gefitinib sensitivity and anti-tumor efficacy in lung cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- A study of high dose furmonertinib in EGFR exon 20 insertion mutation-positive advanced non-small cell lung cancer.Frontiers in oncology · 2024Article
- Real-World Data Presenting the Descriptive Analysis of the Use of Tyrosine Kinase Inhibitors (TKIs) Among Metastatic Non-Small-Cell Lung Cancer (mNSCLC) Patients in Qatar: A Nationwide Retrospective Cohort Study.Clinical Medicine Insights. Oncology · 2024Article
- The rational application of liquid biopsy based on next-generation sequencing in advanced non-small cell lung cancer.Cancer medicine · 2023Article
- Genetic profiling of hormone-sensitive and castration-resistant prostate cancers and identification of genetic mutations prone to castration-resistant prostate cancer.Prostate cancer and prostatic diseases · 2023Article
- Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC?Journal of clinical medicine · 2023Review
- KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration.Journal of clinical medicine · 2023Review
- Acquired Concurrent EGFR T790M and Driver Gene Resistance From EGFR-TKIs Hampered Osimertinib Efficacy in Advanced Lung Adenocarcinoma: Case Reports.Frontiers in pharmacology · 2022Article
- TP53 Co-Mutations in Advanced EGFR-Mutated Non-Small Cell Lung Cancer: Prognosis and Therapeutic Strategy for Cancer Therapy.Frontiers in oncology · 2022Review
- Review
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 15 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNon-small cell lung cancer (NSCLC) patients treated with first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) almost always acquire resistance, and the development of novel techniques analyzing circulating tumor DNA (ctDNA) have made it possible for liquid biopsy to detect genetic alterations from limited amount of DNA with less invasiveness. While a large amount of patients with EGFR exon 21 p.Thr790 Met (T790M) benefited from osimertinib treatment, acquired resistance to osimertinb has subsequently become a growing challenge.
methodsWe performed tissue and liquid rebiopsy on 50 patients with EGFR-mutant NSCLC who acquired resistance to first-generation EGFR-TKIs. Plasma samples underwent droplet digital PCR (ddPCR) and next-generation sequencing (NGS) examinations. Corresponding tissue samples underwent NGS and Cobas
resultsOf the 50 patients evaluated, the mutation detection rates of liquid biopsy group and tissue biopsy group demonstrated no significant differences (41/48, 85.4% vs. 44/48, 91.7%; OR=0.53, 95% CI=0.15 to 1.95). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 78.3% (36/46, 95% CI=0.39 to 2.69). Moreover, our results showed that almost half of the patients (46%, 23/50) resistant to first-generation EGFR-TKI harbored p.Thr790 Met (T790M) mutation. 82.6% (19/23) of the T790M positive patients were analyzed by liquid biopsy and 60.9% (14/23) by tumor tissue sequencing. Meanwhile, a wide range of uncommon mutations was detected, and novel mechanisms of osimertinib resistance were discovered. In addition, 16.7% (2/12) of the T790M positive patients with either TP53 R237C or KRAS G12V failed to benefit from the subsequent osimertinib treatment.
conclusionOur results emphasized that liquid biopsy is applicable to analyze the drug resistance mechanisms of NSCLC patients treated with EGFR-TKIs. Moreover, we discovered two uncommon mutations, TP53 R273C and KRAS G12V, which attenuates the effectiveness of osimertinib.
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