ArticleNeoplasia (New York, N.Y.)2017
Digoxin Plus Trametinib Therapy Achieves Disease Control in BRAF Wild-Type Metastatic Melanoma Patients.
Article in Neoplasia (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Pooled it
- Pharmacogenomic Synthetic Lethal Screens Reveal Hidden Vulnerabilities and New Therapeutic Approaches for Treatment of NF1-Associated Tumors.Molecular cancer therapeutics · 2026Article
- Repurposing of NKA inhibitors ('cardiac glycosides'): a critical analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Identification and therapeutic investigation of biomarker genes underpinning hepatocellular carcinoma: anFrontiers in bioinformatics · 2025Article
- Differential bone morphology and hypoxia activity in skeletal metastases of ERCommunications biology · 2024Article
- Digoxin and its NaBioorganic & medicinal chemistry · 2024Review
- Emerging dimensions of autophagy in melanoma.Autophagy · 2024Review
- New hemisynthetic derivatives of sphaeropsidin phytotoxins triggering severe endoplasmic reticulum swelling in cancer cells.Scientific reports · 2024Article
- Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice.Cancer cell international · 2023Review
- Pharmaco-Toxicological Assessment of the Combined Cytotoxic Effects of Digoxin and Betulinic Acid in Melanoma Cells.Life (Basel, Switzerland) · 2022Article
- Digitoxin Affects Metabolism, ROS Production and Proliferation in Pancreatic Cancer Cells Differently Depending on the Cell Phenotype.International journal of molecular sciences · 2022Article
- A novel 7 RNA-based signature for prediction of prognosis and therapeutic responses of wild-type BRAF cutaneous melanoma.Biological procedures online · 2022Article
- Spatiotemporal trends of the global burden of melanoma in 204 countries and territories from 1990 to 2019: Results from the 2019 global burden of disease study.Neoplasia (New York, N.Y.) · 2022Article
- Optimizing Drug Response Study Design in Patient-Derived Tumor Xenografts.Cancer informatics · 2022Article
- The botanical drug PBI-05204, a supercritical COFrontiers in pharmacology · 2022Article
- Digoxin exerts anticancer activity on human nonsmall cell lung cancer cells by blocking PI3K/Akt pathway.Bioscience reports · 2021Article
- Clinical significance of P-class pumps in cancer.Oncology letters · 2021Review
- Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics.Biomolecules · 2021Review
- The Role of Senescent Cells in Acquired Drug Resistance and Secondary Cancer in BRAFi-Treated Melanoma.Cancers · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
This is the first prospective study of a combination therapy involving a cardenolide and a MEK inhibitor for metastatic melanoma. Whereas BRAF mutant melanomas can exhibit profound responses to treatment with BRAF and MEK inhibitors, there are fewer options for BRAF wild-type melanomas. In preclinical studies, we discovered that cardenolides synergize with MEK inhibitor to promote the regression of patient-derived xenografts irrespective of BRAF mutation status. We therefore conducted a phase 1B study of digoxin 0.25 mg and trametinib 2 mg given orally once daily in 20 patients with advanced, refractory, BRAF wild-type melanomas. The most common adverse events were rash, diarrhea, nausea, and fatigue. The response rate was 4/20 or 20% with response durations of 2, 4, 6, and 8 months. The disease control rate (including partial responses and stable disease) was 13/20 or 65% of patients, including 5/6 or 83% of patients with NRAS mutant melanomas and 8/14 or 57% of NRAS wild-type melanomas. Patients with stable disease had disease control for 2, 2, 2, 4, 5, 6, 7, 10, and 10 months. Xenografts from four patients recapitulated the treatment responses observed in patients. Based on these pilot results, an expansion arm of digoxin plus MEK inhibitor is warranted for NRAS mutant metastatic melanoma patients who are refractory or intolerant of immunotherapy. KEY POINTS: Digoxin plus trametinib is well tolerated and achieves a high rate of disease control in BRAF wild-type metastatic melanoma patients.
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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.