ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2022
Concurrent TP53 Mutations Facilitate Resistance Evolution in EGFR-Mutant Lung Adenocarcinoma.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 145 citations in OpenAlex.
- Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Gefitinib Plus Chemotherapy vs Gefitinib Alone in Untreated EGFR-Mutant Non-Small Cell Lung Cancer in Patients With Brain Metastases: The GAP BRAIN Open-Label, Randomized, Multicenter, Phase 3 Study.JAMA network open · 2023Trial
- Impact of differentTranslational lung cancer research · 2026Article
- Landscape of Chinese Lung Cancer Patients With Compound Mutations and Acquired Resistance Alterations: A Retrospective Study.International journal of cancer · 2026Article
- Second-Line Therapy Following Osimertinib in Metastatic EGFR-Mutated Non-Small-Cell Lung Cancer at an Academic Medical Center.Cancer reports (Hoboken, N.J.) · 2026Article
- Genetic insights into lung squamous cell carcinoma: howTranslational cancer research · 2026Article
- Novel Co-Occurrence of GermlineInternational journal of molecular sciences · 2026Article
- Targeting ClassicalCancers · 2026Review
- Risk Stratification and Strategies Towards Front-Line Therapy of EGFR-Mutant NSCLC: A Narrative Review.Cancers · 2026Review
- Genomic Insights into Innate Resistance in Early-Stage EGFR-Mutant Non-Small Cell Lung Cancer: A Comprehensive Analysis of Next-Generation Sequencing Data.Cancer research and treatment · 2026Observational
- Association of TP53 gain-of-function mutations with early osimertinib resistance in epidermal growth factor receptor-mutant lung adenocarcinoma.ESMO open · 2026Article
- The landscape of MET alterations in non-small cell lung cancer in Southeastern China: a real-world study.BMC cancer · 2026Article
- Novel strategy of pemetrexed combined with localized therapy: breakthrough impact of long-term maintenance regimen on patient survival-a case report.Journal of medical case reports · 2026Article
- Recurrent cancer-associated ERBB4 mutations are transforming and confer resistance to targeted therapies.Molecular oncology · 2026Article
- Prolonged complete metabolic response to chemotherapy combined with amivantamab with high grade cutaneous toxicity after osimertinib resistance in an uncommonTranslational lung cancer research · 2026Article
- Review
- EBF3 suppresses lung adenocarcinoma progression and immune evasion via transcriptional repression of CCL24.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Comparison of tissue acquisition techniques for Next-Generation Sequencing of non-small cell lung cancer (NSCLC).BMJ open respiratory research · 2026Article
- EGFR G719X + S768I co-mutations in NSCLC: genomic landscape and differential responses to EGFR-TKIs in a large real-world cohort.BMC cancer · 2026Article
- KIF18B Is Essential for Lung Adenocarcinoma Progression Through the E2F Transcriptional Network.International journal of molecular sciences · 2026Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
introductionPatients with EGFR-mutant NSCLC experience variable duration of benefit on EGFR tyrosine kinase inhibitors. The effect of concurrent genomic alterations on outcome has been incompletely described.
methodsIn this retrospective study, targeted next-generation sequencing data were collected from patients with EGFR-mutant lung cancer treated at the Dana-Farber Cancer Institute. Clinical data were collected and correlated with somatic mutation data. Associations between TP53 mutation status, genomic features, and mutational processes were analyzed.
resultsA total of 269 patients were identified for inclusion in the cohort. Among 185 response-assessable patients with pretreatment specimens, TP53 alterations were the most common event associated with decreased first-line progression-free survival and decreased overall survival, along with DNMT3A, KEAP1, and ASXL1 alterations. Reduced progression-free survival on later-line osimertinib in 33 patients was associated with MET, APC, and ERBB4 alterations. Further investigation of the effect of TP53 alterations revealed an association with worse outcomes even in patients with good initial radiographic response, and faster acquisition of T790M and other resistance mechanisms. TP53-mutated tumors had higher mutational burdens and increased mutagenesis with exposure to therapy and tobacco. Cell cycle alterations were not independently predictive, but portended worse OS in conjunction with TP53 alterations.
conclusionsTP53 alterations associate with faster resistance evolution independent of mechanism in EGFR-mutant NSCLC and may cooperate with other genomic events to mediate acquisition of resistance mutations to EGFR tyrosine kinase inhibitors.
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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.