ArticleCell death discovery2022
Targeting nicotinamide N-methyltransferase overcomes resistance to EGFR-TKI in non-small cell lung cancer cells.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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
17 citing papers in PubMed, 20 citations in OpenAlex.
- Early radiotherapy delays acquired gefitinib resistance in EGFR-mutant NSCLC by suppressing c-FOS-associated survival signaling.Respiratory research · 2026Article
- NNMT and the methylation sink: integrating metabolism, epigenetics and immunity in cancer.BMC medicine · 2026Review
- Gene dependency-informed inference of response to targeted cancer therapies.Nature communications · 2026Article
- Nicotinamide N-methyltransferase as a therapeutic target in taxane-resistant castration-resistant prostate cancer.Cell death discovery · 2026Article
- Article
- Spatiotemporal Heterogeneity of Tumor Glucose Metabolism Reprogramming: From Single-Cell Mechanisms to Precision Interventions.International journal of molecular sciences · 2025Review
- Antisense oligonucleotide targeting nicotinamide N-methyltransferase exhibits antitumor effects.Molecular therapy. Nucleic acids · 2025Article
- Article
- Integrative multi-omics identifies AP-1 transcription factor as a targetable mediator of acquired osimertinib resistance in non-small cell lung cancer.Cell death & disease · 2025Article
- NNMT promotes acquired EGFR-TKI resistance by forming EGR1 and lactate-mediated double positive feedback loops in non-small cell lung cancer.Molecular cancer · 2025Article
- Single-Cell RNA Sequencing in Unraveling Acquired Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: New Perspectives.International journal of molecular sciences · 2025Review
- Nicotinamide N-methyltransferase negatively regulates metastasis-promoting property of cancer-associated fibroblasts in lung adenocarcinoma.Cancer communications (London, England) · 2025Article
- A systematic evaluation of quenching, extraction and analysis procedures for metabolomics study of the mechanism of QYSLD intervention in A549 cells.Analytical and bioanalytical chemistry · 2024Article
- MYC expression and fatty acid oxidation in EGFR-TKI acquired resistance.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- The Role of Proteomics and Phosphoproteomics in the Discovery of Therapeutic Targets and Biomarkers in Acquired EGFR-TKI-Resistant Non-Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
- FBP1 induced by β-elemene enhances the sensitivity of gefitinib in lung cancer.Thoracic cancer · 2023Article
- Systematic pan-cancer analysis of the nicotinamide n-methyltransferase in human cancer.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Activating mutations of epidermal growth factor receptor (EGFR) contributes to the progression of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitor (TKI)-targeted therapy has become the standard treatment for NSCLC patients with EGFR-mutations. However, acquired resistance to these agents remains a major obstacle for managing NSCLC. Here, we investigated a novel strategy to overcome EGFR TKI resistance by targeting the nicotinamide N-methyltransferase (NNMT). Using iTRAQ-based quantitative proteomics analysis, we identified that NNMT was significantly increased in EGFR-TKI-resistant NSCLC cells. Moreover, we found that NNMT expression was increased in EGFR-TKI-resistant NSCLC tissue samples, and higher levels were correlated with shorter progression-free survival in EGFR-TKI-treated NSCLC patients. Knockdown of NNMT rendered EGFR-TKI-resistant cells more sensitive to EGFR-TKI, whereas overexpression of NNMT in EGFR-TKI-sensitive cells resulted in EGFR-TKI resistance. Mechanically, upregulation of NNMT increased c-myc expression via SIRT1-mediated c-myc deacetylation, which in turn promoted glycolysis and EGFR-TKI resistance. Furthermore, we demonstrated that the combination of NNMT inhibitor and EGFR-TKI strikingly suppressed the growth of EGFR-TKI-resistant NSCLC cells both in vitro and in vivo. In conclusion, our research indicated that NNMT overexpression is important for acquired resistance to EGFR-TKI and that targeting NNMT might be a potential therapeutic strategy to overcome resistance to EGFR TKI.
Identifiers
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.