ArticleOncotarget2015
NF-κB drives acquired resistance to a novel mutant-selective EGFR inhibitor.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Atlas-Guided Nanocarrier Strategies Targeting Spatial NTRK2/MAPK Signaling in EGFR-TKI-Resistant Niches of Esophageal Squamous Cell Carcinoma.Pharmaceutics · 2026Review
- The STAT3-ZEB1 axis contributes to CCL2-mediated resistance to osimertinib in lung cancer.Frontiers in oncology · 2026Article
- Targeting the NF-κB Pathway in Cancer: Mechanisms, Resistance, and Therapeutic Potential Across Tumor Types.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Article
- Preclinical Models for Acquired Resistance to Third-Generation EGFR Inhibitors in NSCLC: Functional Studies and Drug Combinations Used to Overcome Resistance.Frontiers in oncology · 2022Review
- Preclinical Models for the Study of Lung Cancer Pathogenesis and Therapy Development.Cold Spring Harbor perspectives in medicine · 2021Review
- Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- miR-146b-5p Enhances the Sensitivity of NSCLC to EGFR Tyrosine Kinase Inhibitors by Regulating the IRAK1/NF-κB Pathway.Molecular therapy. Nucleic acids · 2020Article
- Synergistic effects of Bcl-2 inhibitors with AZD9291 on overcoming the acquired resistance of AZD9291 in H1975 cells.Archives of toxicology · 2020Article
- Drug Sensitivity and Allele Specificity of First-Line Osimertinib ResistanceCancer research · 2020Article
- CDRgator: An Integrative Navigator of Cancer Drug Resistance Gene Signatures.Molecules and cells · 2019Article
- CX Chemokine Receptor 7 Contributes to Survival ofCancers · 2019Article
- Personalized Prediction of Acquired Resistance to EGFR-Targeted Inhibitors Using a Pathway-Based Machine Learning Approach.Cancers · 2019Article
- Phase I study of the combination of quinacrine and erlotinib in patients with locally advanced or metastatic non small cell lung cancer.Investigational new drugs · 2018Article
- Emerging application of genomics-guided therapeutics in personalized lung cancer treatment.Annals of translational medicine · 2018Review
- Optimization Of Cancer Treatment Through Overcoming Drug Resistance.Journal of cancer research and oncobiology · 2018Article
- Review
- Plasma microRNA alterations between EGFR-activating mutational NSCLC patients with and without primary resistance to TKI.Oncotarget · 2017Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
The clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) harbouring activating EGFR mutations is limited by the emergence of acquired resistance, mostly ascribed to the secondary EGFR-T790M mutation. Selective EGFR-T790M inhibitors have been proposed as a new, extremely relevant therapeutic approach. Here, we demonstrate that the novel irreversible EGFR-TKI CNX-2006, a structural analog of CO-1686, currently tested in a phase-1/2 trial, is active against in vitro and in vivo NSCLC models expressing mutant EGFR, with minimal effect on the wild-type receptor. By integration of genetic and functional analyses in isogenic cell pairs we provide evidence of the crucial role played by NF-κB1 in driving CNX-2006 acquired resistance and show that NF-κB activation may replace the oncogenic EGFR signaling in NSCLC when effective and persistent inhibition of the target is achieved in the presence of the T790M mutation. In this context, we demonstrate that the sole, either genetic or pharmacologic, inhibition of NF-κB is sufficient to reduce the viability of cells that adapted to EGFR-TKIs. Overall, our findings support the rational inhibition of members of the NF-κB pathway as a promising therapeutic option for patients who progress after treatment with novel mutant-selective EGFR-TKIs.
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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.