ArticleOncotarget2015
Molecular heterogeneity assessment by next-generation sequencing and response to gefitinib of EGFR mutant advanced lung adenocarcinoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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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
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- 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
- Identification of Key Transcription Factors Associated with Lung Squamous Cell Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2017Pooled it
- Use of Gefitinib in EGFR-Amplified Refractory Solid Tumors: An Open-Label, Single-Arm, Single-Center Prospective Pilot Study.Targeted oncology · 2020Trial
- 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
- Is there a prognostic difference among stage I lung adenocarcinoma patients with different BRAF-mutation status?Thoracic cancer · 2024Article
- Tissue- and liquid-biopsy based NGS profiling in advanced non-small-cell lung cancer in a real-world setting: the IMMINENT study.Frontiers in oncology · 2024Article
- Heterogeneous distribution ofRespiratory medicine case reports · 2023Article
- Concomitant TP53 mutation in early-stage resected EGFR-mutated non-small cell lung cancer: a narrative approach in a genetically admixed Brazilian cohort.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
- Concurrent TP53 mutations predict a poor prognosis of EGFR-mutant NSCLCs treated with TKIs: An updated systematic review and meta-analysis.Oncology letters · 2022Article
- The Role ofCancers · 2022Review
- Article
- Downregulation of REV-ERBα is associated with the progression of lung adenocarcinoma.Annals of translational medicine · 2022Article
- Treating disease progression with osimertinib in EGFR-mutated non-small-cell lung cancer: novel targeted agents and combination strategies.ESMO open · 2021Review
- Intercellular transfer of exosomal wild type EGFR triggers osimertinib resistance in non-small cell lung cancer.Molecular cancer · 2021Article
- Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: impact of STK11, KRAS and TP53 mutations and co-mutations on outcome.Translational lung cancer research · 2021Article
- Oncogene-Addicted Non-Small-Cell Lung Cancer: Treatment Opportunities and Future Perspectives.Cancers · 2020Review
- Detection of Low-FrequencyFrontiers in oncology · 2020Article
- Maximum allele frequency observed in plasma: A potential indicator of liquid biopsy sensitivity.Oncology letters · 2019Article
- Clinical outcome of treatment of metastatic non-small cell lung cancer in patients harboring uncommon EGFR mutation.BMC cancer · 2019Article
- Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer molecular heterogeneity might explain the variable response of EGFR mutant lung adenocarcinomas to tyrosine kinase inhibitors (TKIs). We assessed the mutational status of 22 cancer genes by next-generation sequencing (NGS) in poor, intermediate or good responders to first-line gefitinib. Clinical outcome was correlated with Additional Coexisting Mutations (ACMs) and the EGFR Proportion of Mutated Alleles (PMA). Thirteen ACMs were found in 10/17 patients: TP53 (n=6), KRAS (n=2), CTNNB1 (n=2), PIK3CA, SMAD4 and MET (n=1 each). TP53 mutations were exclusive of poor/intermediate responders (66.7% versus 0, p=0.009). Presence of ACMs significantly affected both PFS (median 3.0 versus 12.3 months, p=0.03) and survival (3.6 months versus not reached, p=0.03). TP53 mutation was the strongest negative modifier (median PFS 4.0 versus 14.0 months). Higher EGFR PMA was present in good versus poor/intermediate responders. Median PFS and survival were longer in patients with EGFR PMA ≥0.36 (12.0 versus 4.0 months, p=0.31; not reached versus 18.0 months, p=0.59). Patients with an EGFR PMA ≥0.36 and no ACMs fared significantly better (p=0.03), with a trend towards increased survival (p=0.06). Our exploratory data suggest that a quantitative (PMA) and qualitative (ACMs) molecular heterogeneity assessment using NGS might be useful for a better selection of patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.