ArticleNPJ precision oncology2024
TP53 gain-of-function mutations promote osimertinib resistance via TNF-α-NF-κB signaling in EGFR-mutated lung cancer.
Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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
23 citing papers in PubMed, 34 citations in OpenAlex.
- Osimertinib plus anlotinib in untreated, EGFR-mutated, advanced non-small-cell lung cancer with concurrent alterations: a multicenter phase II study.The oncologist · 2026Trial
- 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
- Development of a structurally distinct TopBP1 inhibitor that enhances PARP blockade and reverses osimertinib resistance.Science advances · 2026Article
- Risk Stratification and Strategies Towards Front-Line Therapy of EGFR-Mutant NSCLC: A Narrative Review.Cancers · 2026Review
- Association of TP53 gain-of-function mutations with early osimertinib resistance in epidermal growth factor receptor-mutant lung adenocarcinoma.ESMO open · 2026Article
- Interleukin-1α-Mediated Activation of TNF-α/NF-κB Signaling Confers Resistance to Osimertinib in EGFR-Mutant Non-Small-Cell Lung Cancer.Thoracic cancer · 2026Article
- BRCA1/2 Reversion Mutations in Japanese Patients with Metastatic Breast Cancer Progressing on Olaparib: OLIVE (WJOG15321B).Breast cancer (Tokyo, Japan) · 2026Observational
- LncRNA FEZF1-AS1 promotes the tumorigenesis and suppresses ferroptosis in non-small cell lung cancer through the TNF-α/NF-κB pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Osimertinib activates a TGF-β2-dependent secretory program that drives lung adenocarcinoma progression.The Journal of clinical investigation · 2026Article
- Therapeutic Potential ofInternational journal of general medicine · 2026Article
- Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC - mechanisms and evolving treatment approaches.Nature reviews. Clinical oncology · 2026Review
- Prognostic impact of the lymph node yield on survival in patients with stage I lung adenocarcinoma receiving sublobar resection.Frontiers in molecular biosciences · 2026Article
- Leveraging Acquired EGFR-TKI-Resistant Models to Identify MUC16 as a Therapeutic Vulnerability in Lung Adenocarcinoma.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Long non-coding RNA AFAP1-AS1 promotes alternative splicing of AXIN2 by facilitating SRSFs phase separation to induce drug resistance in lung adenocarcinoma.Molecular cancer · 2025Article
- IFITM3-MET interaction drives osimertinib resistance through AKT pathway activation in EGFR-mutant non-small cell lung cancer.Molecular cancer · 2025Article
- Molecular Characteristics and Treatment Implications of TP53 Gain-of-Function Mutations in Non-Small Cell Lung Cancer.Cancer medicine · 2025Article
- DynaTag for efficient mapping of transcription factors in low-input samples and at single-cell resolution.Nature communications · 2025Article
- Identification of a gene score related to antigen processing and presentation machinery for predicting prognosis in head and neck squamous cell carcinoma and its potential implications for immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Identification and validation of a lenvatinib resistance-related prognostic signature in HCC, in which PFKFB4 contributes to tumor progression and lenvatinib resistance.BMC gastroenterology · 2025Article
- Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
EGFR tyrosine kinase inhibitors (TKIs) are effective against EGFR-mutated lung cancer, but tumors eventually develop resistance to these drugs. Although TP53 gain-of-function (GOF) mutations promote carcinogenesis, their effect on EGFR-TKI efficacy has remained unclear. We here established EGFR-mutated lung cancer cell lines that express wild-type (WT) or various mutant p53 proteins with CRISPR-Cas9 technology and found that TP53-GOF mutations promote early development of resistance to the EGFR-TKI osimertinib associated with sustained activation of ERK and expression of c-Myc. Gene expression analysis revealed that osimertinib activates TNF-α-NF-κB signaling specifically in TP53-GOF mutant cells. In such cells, osimertinib promoted interaction of p53 with the NF-κB subunit p65, translocation of the resulting complex to the nucleus and its binding to the TNF promoter, and TNF-α production. Concurrent treatment of TP53-GOF mutant cells with the TNF-α inhibitor infliximab suppressed acquisition of osimertinib resistance as well as restored osimertinib sensitivity in resistant cells in association with attenuation of ERK activation and c-Myc expression. Our findings indicate that induction of TNF-α expression by osimertinib in TP53-GOF mutant cells contributes to the early development of osimertinib resistance, and that TNF-α inhibition may therefore be an effective strategy to overcome such resistance in EGFR-mutant lung cancer with TP53-GOF mutations.
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What OpenQuestion holds
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.