ArticleCancer research2016
IKBKE Is a Substrate of EGFR and a Therapeutic Target in Non-Small Cell Lung Cancer with Activating Mutations of EGFR.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Discovery of N8: a novel IKKε inhibitor with potent anticancer activity via cytotoxicity, migration suppression, and autophagy modulation.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Sex and regional effects ofmBio · 2026Article
- Immunogenic cell death and tertiary lymphoid structures jointly define dysregulated antitumor immune states and therapeutic vulnerability in lung adenocarcinoma.Frontiers in immunology · 2026Article
- TBK1 inhibitor amlexanox exerts anti-cancer effects against endometrial cancer by regulating AKT/NF-κB signaling.International journal of biological sciences · 2025Article
- NF-κB in biology and targeted therapy: new insights and translational implications.Signal transduction and targeted therapy · 2024Review
- IKBKE regulates renal cell carcinoma progression and sunitinib resistance through the RRM2-AKT pathway.International journal of biological sciences · 2024Article
- IKBKE phosphorylates and stabilizes Snail to promote breast cancer invasion and metastasis.Cell death and differentiation · 2022Article
- Article
- Silencing IKBKE inhibits the migration and invasion of glioblastoma by promoting Snail1 degradation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- Advances in Immunosuppressive Agents Based on Signal Pathway.Frontiers in pharmacology · 2022Review
- GraphSynergy: a network-inspired deep learning model for anticancer drug combination prediction.Journal of the American Medical Informatics Association : JAMIA · 2021Article
- Amlexanox Enhances Temozolomide-Induced Antitumor Effects in Human Glioblastoma Cells by Inhibiting IKBKE and the Akt-mTOR Signaling Pathway.ACS omega · 2021Article
- I-Oxidative medicine and cellular longevity · 2021Article
- IKBKE enhances TMZ-chemoresistance through upregulation of MGMT expression in glioblastoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Article
- IKBKE activity enhances AR levels in advanced prostate cancer via modulation of the Hippo pathway.Nucleic acids research · 2020Article
- Targeting the IκB Kinase Enhancer and Its Feedback Circuit in Pancreatic Cancer.Translational oncology · 2020Article
- Advances in IKBKE as a potential target for cancer therapy.Cancer medicine · 2020Review
- IKK Epsilon Deficiency Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice by Inhibiting Inflammation, Oxidative Stress, and Apoptosis.Oxidative medicine and cellular longevity · 2020Article
- Targeting IκappaB kinases for cancer therapy.Seminars in cancer biology · 2019Review
- Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
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Abstract
Non-small cell lung cancers (NSCLC) marked by EGFR mutations tend to develop resistance to therapeutic EGFR inhibitors, often due to secondary mutation EGFR(T790M) but also other mechanisms. Here we report support for a rationale to target IKBKE, an IκB kinase family member that activates the AKT and NF-κB pathways, as one strategy to address NSCLC resistant to EGFR inhibitors. While wild-type and mutant EGFR directly interacted with IKBKE, only mutant EGFR phosphorylated IKBKE on residues Y153 and Y179. The unphosphorylatable mutant IKBKE-Y153F/Y179-F that lost kinase activity failed to activate AKT and inhibited EGFR signaling. In clinical specimens of NSCLC with activating mutations of EGFR, we observed elevated levels of phospho-Y153 IKBKE. IKBKE ablation with shRNA or small-molecule inhibitor amlexanox selectively inhibited the viability of NSCLC cells with EGFR mutations in vitro In parallel, we found that these treatments activated the MAPK pathway due to attenuation of an IKBKE feedback mechanism. In vivo studies revealed that combining amlexanox with MEK inhibitor AZD6244 significantly inhibited the xenograft tumor growth of NSCLC cells harboring activating EGFR mutations, including EGFR(T790M) Overall, our findings define IKBKE as a direct effector target of EGFR and provide a therapeutic rationale to target IKBKE as a strategy to eradicate EGFR-TKI-resistant NSCLC cells. Cancer Res; 76(15); 4418-29. ©2016 AACR.
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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.