ArticleCell death & disease2018
Targeting EHMT2 reverses EGFR-TKI resistance in NSCLC by epigenetically regulating the PTEN/AKT signaling pathway.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 76 citations in OpenAlex.
- Comparative Preclinical Evaluation of BIX-01294 and UNC0642 as EHMT2-Targeting Anticancer Agents.Cancers · 2026Article
- AFF4 promotes tumor progression and cisplatin resistance by modulating the PTEN/PI3K/AKT/mTOR axis to accelerate glycolysis in lung adenocarcinoma.Cell & bioscience · 2025Article
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- PTEN-mediated resistance in cancer: From foundation to future therapies.Toxicology reports · 2025Review
- CKAP4 is a potential therapeutic target to overcome resistance to EGFR-TKIs in lung adenocarcinoma.Genes & genomics · 2025Article
- EHMT2-mediated R-loop formation promotes the malignant progression of prostate cancer via activating Aurora B.Clinical and translational medicine · 2025Article
- Efficacy and safety of anlotinib combined with S‑1 as a third‑ or later‑line treatment for advanced non‑small cell lung cancer in China: A systematic review and meta‑analysis.Oncology letters · 2024Article
- PD-L2 drives resistance to EGFR-TKIs: dynamic changes of the tumor immune environment and targeted therapy.Cell death and differentiation · 2024Article
- PARP1 promotes EGFR-TKI drug-resistance via PI3K/AKT pathway in non-small-cell lung cancer.Cancer chemotherapy and pharmacology · 2024Article
- Review
- Cancer epigenetics: from laboratory studies and clinical trials to precision medicine.Cell death discovery · 2024Review
- Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.Frontiers in molecular biosciences · 2024Review
- Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer.Frontiers in oncology · 2024Review
- Histone modifications in drug-resistant cancers: From a cancer stem cell and immune evasion perspective.Experimental & molecular medicine · 2023Review
- ZDHHC2-Mediated AGK Palmitoylation Activates AKT-mTOR Signaling to Reduce Sunitinib Sensitivity in Renal Cell Carcinoma.Cancer research · 2023Article
- Gain-of-function mutations in the catalytic domain ofScience advances · 2023Article
- Novel insights into histone lysine methyltransferases in cancer therapy: From epigenetic regulation to selective drugs.Journal of pharmaceutical analysis · 2023Review
- Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance.Cancers · 2022Review
- Claudin1 decrease induced by 1,25-dihydroxy-vitamin D3 potentiates gefitinib resistance therapy through inhibiting AKT activation-mediated cancer stem-like properties in NSCLC cells.Cell death discovery · 2022Article
- Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). Epigenetic alterations have been shown to be involved in NSCLC oncogenesis; however, their function in EGFR-TKI resistance remains uncharacterized. Here, we found that an EHMT2 inhibitor, UNC0638, can significantly inhibit cell growth and induce apoptosis in EGFR-TKI-resistant NSCLC cells. Additionally, we also found that EHMT2 expression and enzymatic activity levels were elevated in EGFR-TKI-resistant NSCLC cells. Moreover, we determined that genetic or pharmacological inhibition of EHMT2 expression enhanced TKI sensitivity and suppressed migration and tumor sphere formation in EGFR-TKI-resistant NSCLC cells. Further investigation revealed that EHMT2 contributed to PTEN transcriptional repression and thus facilitated AKT pathway activation. The negative relationship between EHMT2 and PTEN was confirmed by our clinical study. Furthermore, we determined that combination treatment with the EHMT2 inhibitor and Erlotinib resulted in enhanced antitumor effects in a preclinical EGFR-TKI-resistance model. We also found that high EHMT2 expression along with low PTEN expression can predict poor overall survival in patients with NSCLC. In summary, our findings showed that EHMT2 facilitated EGFR-TKI resistance by regulating the PTEN/AKT pathway in NSCLC cells, suggesting that EHMT2 may be a target in the clinical treatment of EGFR-TKI-resistant NSCLC.
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