ArticleAntioxidants & redox signaling2016
Targeting Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer by Inducing Epidermal Growth Factor Receptor Degradation via Methionine 790 Oxidation.
Article in Antioxidants & redox signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 79 citations in OpenAlex.
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- Sanguinarine Regulates Tumor-Associated Macrophages to Prevent Lung Cancer Angiogenesis Through the WNT/β-Catenin Pathway.Frontiers in oncology · 2022Article
- Role of NRF2 in Lung Cancer.Cells · 2021Review
- FGFC1 Selectively Inhibits Erlotinib-Resistant Non-Small Cell Lung CancerFrontiers in pharmacology · 2021Article
- Nicotinamide adenine dinucleotide phosphate oxidase inhibitor induces apoptosis on Epstein-Barr virus positive B lymphoma cells.Anatomy & cell biology · 2020Article
- Evodiamine suppresses non-small cell lung cancer by elevating CD8Journal of experimental & clinical cancer research : CR · 2020Article
- New Target Therapies in Advanced Non-Small Cell Lung Cancer: A Review of the Literature and Future Perspectives.Journal of clinical medicine · 2020Review
- The synthesis and biological evaluation of sanguinarine derivatives as anti-non-small cell lung cancer agents.RSC medicinal chemistry · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been developed to treat non-small cell lung cancer (NSCLC) patients with EGFR mutation, but TKI resistance is common. Almost half of the acquired resistance patients are due to additional T790M mutation on EGFR (EGFR(T790M)), thus overcoming TKI resistance is important. In this study, we aim to investigate the role of reactive oxygen species (ROS) in TKI resistance as well as the molecular and biological effects of EGFR(T790M) after redox manipulation.
resultsThe basal ROS levels in EGFR(T790M)-containing TKI-resistant NSCLC cell lines were substantially high. Sixty-three human lung tumors showed higher NADPH oxidase isoform 2 (NOX2) expression than normal lung tissues, which may contribute to high basal ROS in cancer and poor survival. Interestingly, only NOX3 was upregulated by sanguinarine, a pharmacological agent to elevate ROS, and resulted in EGFR overoxidation, degradation, and apoptosis. By contrast, such responses were lacking in EGFR(WT) cells. Selective EGFR(T790M) degradation was manipulated by redox imbalance between NOX3 and methionine reductase A (MsrA). Furthermore, the in vivo tumor suppression effect of sanguinarine, NOX3 upregulation, and EGFR degradation were confirmed. INNOVATION: We have found a new treatment strategy to overcome TKI resistance by selectively inducing EGFR(T790M) degradation via specific stimulation of methionine 790 (M790) oxidation. It can be achieved via manipulating redox imbalance between NOX3 and MsrA.
conclusionTargeting EGFR by elevating ROS and redox imbalance is a potential new strategy to develop a new EGFR inhibitor for TKI-resistant patients with a wide therapeutic window between EGFR(T790M) and EGFR(WT).
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