ArticleScientific reports2016
Cardiac glycosides display selective efficacy for STK11 mutant lung cancer.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
24 citing papers in PubMed, 38 citations in OpenAlex.
- Review
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- A cytochrome P450 CYP87A4 imparts sterol side-chain cleavage in digoxin biosynthesis.Nature communications · 2023Article
- An updated pharmacological insight into calotropin as a potential therapeutic agent in cancer.Frontiers in pharmacology · 2023Review
- Chemistry and the Potential Antiviral, Anticancer, and Anti-Inflammatory Activities of Cardiotonic Steroids Derived from Toads.Molecules (Basel, Switzerland) · 2022Review
- Sodium Pump Na + /K + ATPase Subunit α1-Targeted Positron Emission Tomography Imaging of Hepatocellular Carcinoma in Mouse Models.Molecular imaging and biology · 2022Article
- Q-omics: Smart Software for Assisting Oncology and Cancer Research.Molecules and cells · 2021Article
- Anticancer and Antiviral Properties of Cardiac Glycosides: A Review to Explore the Mechanism of Actions.Molecules (Basel, Switzerland) · 2020Review
- Triple-Negative Breast Cancer Cells Exhibit Differential Sensitivity to Cardenolides fromJournal of natural products · 2020Article
- Overexpression and Selective Anticancer Efficacy ofMolecules and cells · 2019Article
- Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy.Nature reviews. Cancer · 2019Review
- Metformin and tenovin-6 synergistically induces apoptosis through LKB1-independent SIRT1 down-regulation in non-small cell lung cancer cells.Journal of cellular and molecular medicine · 2019Article
- Potential Anticancer Agents Characterized from Selected Tropical Plants.Journal of natural products · 2019Review
- A novel three-dimensional high-throughput screening approach identifies inducers of a mutant KRAS selective lethal phenotype.Oncogene · 2018Article
- Ouabain suppresses the growth and migration abilities of glioma U‑87MG cells through inhibiting the Akt/mTOR signaling pathway and downregulating the expression of HIF‑1α.Molecular medicine reports · 2018Article
- Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.Oncotarget · 2018Article
- Digoxin enhances radiation response in radioresistant A549 cells by reducing protein phosphatase 2A.Bioscience reports · 2017Article
- Anticancer and Immunogenic Properties of Cardiac Glycosides.Molecules (Basel, Switzerland) · 2017Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Although STK11 (LKB1) mutation is a major mediator of lung cancer progression, targeted therapy has not been implemented due to STK11 mutations being loss-of-function. Here, we report that targeting the Na(+)/K(+)-ATPase (ATP1A1) is synthetic lethal with STK11 mutations in lung cancer. The cardiac glycosides (CGs) digoxin, digitoxin and ouabain, which directly inhibit ATP1A1 function, exhibited selective anticancer effects on STK11 mutant lung cancer cell lines. Restoring STK11 function reduced the efficacy of CGs. Clinically relevant doses of digoxin decreased the growth of STK11 mutant xenografts compared to wild type STK11 xenografts. Increased cellular stress was associated with the STK11-specific efficacy of CGs. Inhibiting ROS production attenuated the efficacy of CGs, and STK11-AMPK signaling was important in overcoming the stress induced by CGs. Taken together, these results show that STK11 mutation is a novel biomarker for responsiveness to CGs. Inhibition of ATP1A1 using CGs warrants exploration as a targeted therapy for STK11 mutant lung cancer.
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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.