ArticlePloS one2020
Targeting NPL4 via drug repositioning using disulfiram for the treatment of clear cell renal cell carcinoma.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Drug repurposing as a promising therapeutic strategy against renal cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- Cuproptosis in inflammation and cancer: molecular mechanisms and therapeutic targets.Molecular cancer · 2026Review
- NPLOC4 Inhibition Remodels Tumor Microenvironment via M2-to-M1 Macrophage Reprogramming and Boosts Anti-PD-1 Response in Liver Cancer.International journal of biological sciences · 2026Article
- A novel approach to enhance glioblastoma multiforme treatment efficacy: non-coding RNA targeted therapy and adjuvant approaches.Clinical epigenetics · 2025Review
- In silico research of coagulation- and fibrinolysis-related genes for predicting prognosis of clear cell renal cell carcinoma.Translational andrology and urology · 2025Article
- Unveiling the Cuproptosis in Colitis and Colitis-Related Carcinogenesis: A Multifaceted Player and Immune Moderator.Research (Washington, D.C.) · 2025Review
- Article
- NPLOC4 is a potential target and a poor prognostic signature in lung squamous cell carcinoma.Scientific reports · 2023Article
- The immunomodulatory function and antitumor effect of disulfiram: paving the way for novel cancer therapeutics.Discover oncology · 2023Review
- Disulfiram/Copper Induces Immunogenic Cell Death and Enhances CD47 Blockade in Hepatocellular Carcinoma.Cancers · 2022Article
- The metabolomic landscape plays a critical role in glioma oncogenesis.Cancer science · 2022Review
- A drug repurposing strategy for overcoming human multiple myeloma resistance to standard-of-care treatment.Cell death & disease · 2022Article
- Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways.Bioengineered · 2022Article
- The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance.Frontiers in cellular and infection microbiology · 2022Article
- Possible Therapeutic Potential of Disulfiram for Multiple Myeloma.Current oncology (Toronto, Ont.) · 2021Review
- Disulfiram: a novel repurposed drug for cancer therapy.Cancer chemotherapy and pharmacology · 2021Review
- Recent Advances in Repurposing Disulfiram and Disulfiram Derivatives as Copper-Dependent Anticancer Agents.Frontiers in molecular biosciences · 2021Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The alcohol-abuse drug disulfiram has antitumor effects against diverse cancer types via inhibition of the ubiquitin-proteasome protein nuclear protein localization protein 4 (NPL4). However, the antitumor effects of NPL4 and disulfiram in clear cell renal cell carcinoma (ccRCC) are unclear. Here, we evaluated the therapeutic potential of targeting the ubiquitin-proteasome pathway using disulfiram and RNA interference and investigated the mechanisms underlying disulfiram in ccRCC. According to data from The Cancer Genome Atlas, NPL4 mRNA expression was significantly upregulated in clinical ccRCC samples compared with that in normal kidney samples, and patients with high NPL4 expression had poor overall survival compared with patients with low NPL4 expression. Disulfiram and NPL4 siRNA inhibited ccRCC cell proliferation in vitro, and disulfiram inhibited ccRCC tumor growth in a xenograft model. Synergistic antiproliferative effects were observed for combination treatment with disulfiram and sunitinib in vitro and in vivo. In RCC cells from mice treated with disulfiram and/or sunitinib, several genes associated with serine biosynthesis and aldose reductase were downregulated in cells treated with disulfiram or sunitinib alone and further downregulated in cells treated with both disulfiram and sunitinib. These findings provided insights into the mechanisms of disulfiram and suggested novel therapeutic strategies for RCC treatment.
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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.