ArticleNature communications2016
Synergistic effects of ion transporter and MAP kinase pathway inhibitors in melanoma.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 69 citations in OpenAlex.
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Pharmacogenomic Synthetic Lethal Screens Reveal Hidden Vulnerabilities and New Therapeutic Approaches for Treatment of NF1-Associated Tumors.Molecular cancer therapeutics · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Target Identification of Marine Natural Product Odoamide:Odoamide Induces Apoptotic Cell Death by Targeting ATPase NaChembiochem : a European journal of chemical biology · 2025Article
- Integrating network pharmacology and transcriptomics to identify solasonine's anti-osteosarcoma targets and experimental validation.Frontiers in oncology · 2025Article
- Identification and therapeutic investigation of biomarker genes underpinning hepatocellular carcinoma: anFrontiers in bioinformatics · 2025Article
- Intron Retention of DDX39A Driven by SNRPD2 is a Crucial Splicing Axis for Oncogenic MYC/Spliceosome Program in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Hypomethylation of ATP1A1 Is Associated with Poor Prognosis and Cancer Progression in Triple-Negative Breast Cancer.Cancers · 2024Article
- ATP1A1 is a promising new target for melanoma treatment and can be inhibited by its physiological ligand bufalin to restore targeted therapy efficacy.Cancer cell international · 2024Article
- Application of calcium overload-based ion interference therapy in tumor treatment: strategies, outcomes, and prospects.Frontiers in pharmacology · 2024Review
- Dihydroartemisinin inhibits liver cancer cell migration and invasion by reducing ATP synthase production through CaMKK2/NCLX.Oncology letters · 2023Article
- Targeted and functional genomics approaches to the mechanism of action of lagunamide D, a mitochondrial cytotoxin from marine cyanobacteria.Biochemical pharmacology · 2023Article
- The role of mitochondria in the resistance of melanoma to PD-1 inhibitors.Journal of translational medicine · 2023Review
- New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders.World journal of gastroenterology · 2023Review
- Advances in mitochondria-centered mechanism behind the roles of androgens and androgen receptor in the regulation of glucose and lipid metabolism.Frontiers in endocrinology · 2023Review
- Monovalent ions and stress-induced senescence in human mesenchymal endometrial stem/stromal cells.Scientific reports · 2022Article
- The Role of Calcium Signaling in Melanoma.International journal of molecular sciences · 2022Review
- The role ofTranslational cancer research · 2021Article
- Personalized oncology and BRAFJournal of cancer research and clinical oncology · 2021Article
- Tumor microenvironment-based screening repurposes drugs targeting cancer stem cells and cancer-associated fibroblasts.Theranostics · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
New therapies are required for melanoma. Here, we report that multiple cardiac glycosides, including digitoxin and digoxin, are significantly more toxic to human melanoma cells than normal human cells. This reflects on-target inhibition of the ATP1A1 Na(+)/K(+) pump, which is highly expressed by melanoma. MEK inhibitor and/or BRAF inhibitor additively or synergistically combined with digitoxin to induce cell death, inhibiting growth of patient-derived melanomas in NSG mice and synergistically extending survival. MEK inhibitor and digitoxin do not induce cell death in human melanocytes or haematopoietic cells in NSG mice. In melanoma, MEK inhibitor reduces ERK phosphorylation, while digitoxin disrupts ion gradients, altering plasma membrane and mitochondrial membrane potentials. MEK inhibitor and digitoxin together cause intracellular acidification, mitochondrial calcium dysregulation and ATP depletion in melanoma cells but not in normal cells. The disruption of ion homoeostasis in cancer cells can thus synergize with targeted agents to promote tumour regression in vivo.
Indexed as
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What OpenQuestion holds
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.