ArticleInternational journal of molecular sciences2020
The Specific IKKε/TBK1 Inhibitor Amlexanox Suppresses Human Melanoma by the Inhibition of Autophagy, NF-κB and MAP Kinase Pathways.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Frontier of Melanoma Treatment: Defeating Immunotherapy Resistance-A Systematic Review.Oncology research · 2026Pooled it
- 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
- The protein kinase IKK epsilon shapes the melanoma tumor microenvironment by modulating angiogenesis and the T-cell immunity.Molecular medicine (Cambridge, Mass.) · 2026Article
- Article
- Development of translational read-through-inducing drugs as novel therapeutic options for patients with Fanconi anemia.Cell death discovery · 2025Article
- Matrix stiffness-induced IKBKE and MAPK8 signaling drives a phenotypic switch from DCIS to invasive breast cancer.Cell communication and signaling : CCS · 2025Article
- TBK1 inhibitor amlexanox exerts anti-cancer effects against endometrial cancer by regulating AKT/NF-κB signaling.International journal of biological sciences · 2025Article
- Advances in mechanisms and challenges in clinical translation of synergistic nanomaterial-based therapies for melanoma.Frontiers in cell and developmental biology · 2025Review
- Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression.Nature communications · 2024Article
- Cytosolic DNA sensors in neurodegenerative diseases: from physiological defenders to pathological culprits.EMBO molecular medicine · 2024Review
- Article
- IKBKE regulates renal cell carcinoma progression and sunitinib resistance through the RRM2-AKT pathway.International journal of biological sciences · 2024Article
- The role of autophagy in hypoxia-induced radioresistance.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2023Review
- Regulatory mechanisms of retinal ganglion cell death in normal tension glaucoma and potential therapies.Neural regeneration research · 2023Review
- Article
- Article
- The role of TBK1 in cancer pathogenesis and anticancer immunity.Journal of experimental & clinical cancer research : CR · 2022Review
- The Interplay between Tumour Microenvironment Components in Malignant Melanoma.Medicina (Kaunas, Lithuania) · 2022Review
- Targeting IKKε in Androgen-Independent Prostate Cancer Causes Phenotypic Senescence and Genomic Instability.Molecular cancer therapeutics · 2022Article
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Authors and funding
9 authors.
Funding
Abstract
Inhibitor-kappaB kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IκB kinases, both described as contributors to tumor growth and metastasis in different cancer types. Several hints indicate that they are also involved in the pathogenesis of melanoma; however, the impact of their inhibition as a potential therapeutic measure in this "difficult-to-treat" cancer type has not been investigated so far. We assessed IKKε and TBK1 expression in human malignant melanoma cells, primary tumors and the metastasis of melanoma patients. Both kinases were expressed in the primary tumor and in metastasis and showed a significant overexpression in tumor cells in comparison to melanocytes. The pharmacological inhibition of IKKε/TBK1 by the approved drug amlexanox reduced cell proliferation, migration and invasion. Amlexanox did not affect the cell cycle progression nor apoptosis induction but significantly suppressed autophagy in melanoma cells. The analysis of potential functional downstream targets revealed that NF-кB and ERK pathways might be involved in kinase-mediated effects. In an in vivo xenograft model in nude mice, amlexanox treatment significantly reduced tumor growth. In conclusion, amlexanox was able to suppress tumor progression potentially by the inhibition of autophagy as well as NF-кB and MAP kinase pathways and might therefore constitute a promising candidate for melanoma therapy.
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