ArticleCell death & disease2020
Combined treatment of mitoxantrone sensitizes breast cancer cells to rapalogs through blocking eEF-2K-mediated activation of Akt and autophagy.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment: A systematic review.PloS one · 2024Pooled it
- Overcoming mTOR Inhibitor Resistance: From Biological Basis to Therapeutic Strategies.Biomedicines · 2026Review
- Targeted Degradation of eEF2K by a Structure-Guided PROTAC Strategy for the Treatment of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- eEF2K-Mediated Stabilization of PCBP2 Promotes Oncogenic mRNA Programs in Triple-Negative Breast Cancer.International journal of biological sciences · 2026Article
- Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha.Nature communications · 2025Article
- Mitoxantrone-liposome SensitizesJournal of Cancer · 2025Article
- Drug Repurposing of Selected Antibiotics: An Emerging Approach in Cancer Drug Discovery.ACS omega · 2024Review
- Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mitoxantrone and abacavir: An ALK protein-targeted in silico proposal for the treatment of non-small cell lung cancer.PloS one · 2024Article
- Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis.Pharmaceutical biology · 2023Article
- Signaling pathways in cancer metabolism: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Impact of silencing eEF2K expression on the malignant properties of chordoma.Molecular biology reports · 2023Article
- Role of cuproptosis-related gene in lung adenocarcinoma.Frontiers in oncology · 2022Article
- Hallmark-guided subtypes of hepatocellular carcinoma for the identification of immune-related gene classifiers in the prediction of prognosis, treatment efficacy, and drug candidates.Frontiers in immunology · 2022Article
- Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase.Frontiers in molecular biosciences · 2021Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Oncogenic activation of the mTOR signaling pathway occurs frequently in tumor cells and contributes to the devastating features of cancer, including breast cancer. mTOR inhibitors rapalogs are promising anticancer agents in clinical trials; however, rapalogs resistance remains an unresolved clinical challenge. Therefore, understanding the mechanisms by which cells become resistant to rapalogs may guide the development of successful mTOR-targeted cancer therapy. In this study, we found that eEF-2K, which is overexpressed in cancer cells and is required for survival of stressed cells, was involved in the negative-feedback activation of Akt and cytoprotective autophagy induction in breast cancer cells in response to mTOR inhibitors. Therefore, disruption of eEF-2K simultaneously abrogates the two critical resistance signaling pathways, sensitizing breast cancer cells to rapalogs. Importantly, we identified mitoxantrone, an admitted anticancer drug for a wide range of tumors, as a potential inhibitor of eEF-2K via a structure-based virtual screening strategy. We further demonstrated that mitoxantrone binds to eEF-2K and inhibits its activity, and the combination treatment of mitoxantrone and mTOR inhibitor resulted in significant synergistic cytotoxicity in breast cancer. In conclusion, we report that eEF-2K contributes to the activation of resistance signaling pathways of mTOR inhibitor, suggesting a novel strategy to enhance mTOR-targeted cancer therapy through combining mitoxantrone, an eEF-2K inhibitor.
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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.