ArticleCell death & disease2016
TC-N19, a novel dual inhibitor of EGFR and cMET, efficiently overcomes EGFR-TKI resistance in non-small-cell lung cancer cells.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- NSC777201 exhibits anticancer activity against colorectal cancer cells by inducing multiple types of cell death.Cancer cell international · 2025Article
- Virtual Screening, Molecular Dynamics Simulation, and Bioactivity Assessment Validate T13074 as a Dual-target EGFR/c-Met Inhibitor.Current medicinal chemistry · 2025Article
- Unveiling the role of PSMA5 in glioma progression and prognosis.Discover oncology · 2024Article
- Unlocking the potential of bispecific ADCs for targeted cancer therapy.Frontiers of medicine · 2024Review
- Article
- Suppression of TNBC metastasis by doxazosin, a novel dual inhibitor of c-MET/EGFR.Journal of experimental & clinical cancer research : CR · 2023Article
- The anti-oncogenic effect of 17-DMAG via the inactivation of HSP90 and MET pathway in osteosarcoma cells.Oncology research · 2023Article
- Leveraging Bulk and Single-Cell RNA Sequencing Data of NSCLC Tumor Microenvironment and Therapeutic Potential of NLOC-15A, A Novel Multi-Target Small Molecule.Frontiers in immunology · 2022Article
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- Article
- In-Silico Evaluation of Genetic Alterations in Ovarian Carcinoma and Therapeutic Efficacy of NSC777201, as a Novel Multi-Target Agent for TTK, NEK2, and CDK1.International journal of molecular sciences · 2021Article
- Relationship between long non-coding RNA PCAT-1 expression and gefitinib resistance in non-small-cell lung cancer cells.Respiratory research · 2021Article
- Article
- Epitranscriptomics and epiproteomics in cancer drug resistance: therapeutic implications.Signal transduction and targeted therapy · 2020Review
- CEP131 knockdown inhibits cell proliferation by inhibiting the ERK and AKT signaling pathways in non-small cell lung cancer.Oncology letters · 2020Article
- Integrative Analysis of Membrane Proteome and MicroRNA Reveals Novel Lung Cancer Metastasis Biomarkers.Frontiers in genetics · 2020Article
- DYRK1A inhibition suppresses STAT3/EGFR/Met signalling and sensitizes EGFR wild-type NSCLC cells to AZD9291.Journal of cellular and molecular medicine · 2019Article
- Non-canonical cMet regulation by vimentin mediates Plk1 inhibitor-induced apoptosis.EMBO molecular medicine · 2019Article
- Therapeutic targeting of the crosstalk between cancer-associated fibroblasts and cancer stem cells.American journal of cancer research · 2019Review
- Shikonin sensitizes wild‑type EGFR NSCLC cells to erlotinib and gefitinib therapy.Molecular medicine reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) show a clinical benefit when used to treat patients with EGFR-mutated non-small-cell lung cancer (NSCLC), but this treatment unfortunately fails in patients with TKI-resistant tumors. We here provide evidence that TC-N19 (N19), a novel dual inhibitor of EGFR and cMET, efficiently overcomes the EGFR-TKI resistance in EGFR-mutated NSCLC cells via simultaneous degradation of both proteins by ubiquitin proteasomes. Comparison with HSP90 inhibitor treatment and knockdown of EGFR and cMET by small hairpin RNAs reveal that the reduction of EGFR and cMET expression by N19 is responsible for overcoming the intrinsic TKI resistance mediated by paxillin (PXN) in high PXN-expressing cells, PXN-overexpressing PC9 cells (PC9-PXN), the EGFR-T790M-mediated TKI resistance in H1975 and CL97 cells, and the acquired resistance to gefitinib in gefitinib-resistant PC9 cells (PC9GR). Annexin V-PI staining assay showed that the induction of apoptosis in NSCLC cells by N19 depended on the reduction in levels of both proteins. Xenograft tumor formation in nude mice induced by a PC9-PXN-stable clone and by PC9GR cells was nearly completely suppressed by N19 treatment, with no changes in animal body weight. MTT assays of normal lung cells and reticulocytes showed no cytotoxicity responses to N19. In summary, N19 may act as a novel dual inhibitor of EGFR and cMET that induces apoptosis in TKI-resistant EGFR-mutated NSCLC cells and suppresses xenograft tumor formation. We suggest that N19 may be a potential new-generation TKI or HSP90 inhibitor used for treatment of NSCLC patients who show resistance to current TKI-targeting therapies.
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