ArticleOncogene2020
Distinct co-acquired alterations and genomic evolution during TKI treatment in non-small-cell lung cancer patients with or without acquired T790M mutation.
Article in Oncogene, 2020. 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 28 papers.
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Who cites it
28 citing papers in PubMed.
- Innovative approaches for lung cancer screening and interception.Nature reviews. Clinical oncology · 2026Review
- Real-world treatment outcomes in South Korean patients with epidermal growth factor receptor-mutant non-small cell lung cancer.The Korean journal of internal medicine · 2025Article
- Plasma-Based Genomic Features Influencing Outcomes of T790M-Positive Non-Small Cell Lung Cancer Receiving Osimertinib.Cancer medicine · 2025Article
- Clinical factors and molecular co-alterations impact outcomes in patients receiving first-line osimertinib for EGFR-mutated non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2025Article
- Targeting Metabolic Vulnerabilities Reveals Hexokinase 2 as a Key Mediator of Resistance to Osimertinib in Non-Small Cell Lung Cancer Models.ACS pharmacology & translational science · 2025Article
- Spatial and multiomics analysis of human and mouse lung adenocarcinoma precursors reveals TIM-3 as a putative target for precancer interception.Cancer cell · 2025Article
- Article
- Multiregional transcriptomic profiling provides improved prognostic insight in localized non-small cell lung cancer.NPJ precision oncology · 2024Article
- Drug Response of Patient-Derived Lung Cancer Cells Predicts Clinical Outcomes of Targeted Therapy.Cancers · 2024Article
- Pathomic Features Reveal Immune and Molecular Evolution From Lung Preneoplasia to Invasive Adenocarcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2023Article
- A subset of VEGFR-TKIs activates AMPK in LKB1-mutant lung cancer.Cancer science · 2023Article
- Unraveling the Impact of Intratumoral Heterogeneity on EGFR Tyrosine Kinase Inhibitor Resistance inInternational journal of molecular sciences · 2023Review
- Rechallenge of immune checkpoint inhibitors in a case with adverse events inducing myasthenia gravis.Journal for immunotherapy of cancer · 2022Article
- RET fusions as primary oncogenic drivers and secondary acquired resistance to EGFR tyrosine kinase inhibitors in patients with non-small-cell lung cancer.Journal of translational medicine · 2022Article
- Impact of clinical and molecular features on efficacy and outcome of patients with non-small cell lung cancer receiving second-line osimertinib.BMC cancer · 2022Article
- Heterogeneity among tumors with acquired resistance to EGFR tyrosine kinase inhibitors harboring EGFR-T790M mutation in non-small cell lung cancer cells.Cancer medicine · 2022Article
- Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study.BMC pulmonary medicine · 2022Article
- Correlation of PD-L1 Expression with Clinicopathological and Genomic Features in Chinese Non-Small-Cell Lung Cancer.Journal of oncology · 2022Article
- High Incidence of C797S Mutation in Patients With Long Treatment History of EGFR Tyrosine Kinase Inhibitors Including Osimertinib.JTO clinical and research reports · 2021Article
- Mutated circulating tumor DNA as a liquid biopsy in lung cancer detection and treatment.Molecular oncology · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
28 authors.
Funding
Abstract
EGFR-mutant non-small-cell lung cancer (NSCLC) patients inevitably develop drug resistance when treated with EGFR tyrosine kinase inhibitors (TKIs). Systematic genetic analysis is important to understand drug-resistant mechanisms; however, the clinical significance of co-occurring genetic alterations at baseline, co-acquired mutations at progressive disease (PD), and the clonal evolution remain underinvestigated. We performed targeted sequencing of pre-treatment and PD tumor samples from 54 EGFR-mutant NSCLC patients. Ten additional patients were sequenced using whole-exome sequencing to infer the clonal evolution patterns. We observed a domain-dependent effect of PIK3CA mutation at baseline on patient progression-free survival (PFS). In addition, at baseline, 9q34.3/19p13.3 (NOTCH1/STK11/GNA11) showed a co-deletion pattern, which was associated with a significantly worse PFS (p = 0.00079). T790M-postive patients with other concurrent acquired oncogenic mutations had a significantly shorter PFS (p = 0.005). Besides acquired T790M mutation, chromosomal instability (CIN) related genes, including AURKA and TP53 alterations, were the most frequently acquired events. CIN significantly increased during TKI treatment in T790M-negative patients and is a candidate resistance mechanism to the first-generation TKIs. Clonal evolution analyses suggest that the composition and relationship among resistant subclones, particularly relationship with T790M subclone, affect patients' outcomes. Overall, our findings of novel co-occurring alterations and clonal evolution patterns can be served as predictive biomarkers to stratify patients and help to better understand the drug-resistant mechanism to TKIs.
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