ArticleOncotarget2016
Auranofin is a potent suppressor of osteosarcoma metastasis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 44 citations in OpenAlex.
- Drug Repurposing in Veterinary Oncology: Myth or Reality?Veterinary sciences · 2025Review
- ROLE OF POLYMORPHISMS IN VEGF AND KDR GENES IN OSTEOSARCOMA SUSCEPTIBILITY: A SYSTEMATIC REVIEW.Acta ortopedica brasileira · 2025Review
- Auranofin Induces ER Stress-Mediated Apoptosis, and Its Combination With Bortezomib Elicits Paraptosis-Like Cell Death in Malignant Canine Mammary Tumour Cells.Veterinary and comparative oncology · 2025Article
- MiR-383 sensitizes osteosarcoma cells to bortezomib treatment via down-regulating PSMB5.Molecular biology reports · 2024Article
- Repurposing auranofin and meclofenamic acid as energy-metabolism inhibitors and anti-cancer drugs.PloS one · 2024Article
- Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy.Biology · 2023Article
- Efficacy of auranofin as an inhibitor of desmoid progression.Scientific reports · 2022Article
- Recent and Ongoing Research into Metastatic Osteosarcoma Treatments.International journal of molecular sciences · 2022Review
- Colchicine as a novel drug for the treatment of osteosarcoma through drug repositioning based on an FDA drug library.Frontiers in oncology · 2022Article
- Effect of tumor-associated macrophages on lncRNA PURPL/miR-363/PDZD2 axis in osteosarcoma cells.Cell death discovery · 2021Article
- Modulation of Mitochondrial Metabolic Reprogramming and Oxidative Stress to Overcome Chemoresistance in Cancer.Biomolecules · 2020Review
- Mechanistic Insights Into the Anticancer Properties of the Auranofin Analog Au(PEtFrontiers in chemistry · 2020Article
- Antineoplastic effects of auranofin in human pancreatic adenocarcinoma preclinical models.Surgery open science · 2019Article
- A Retrospective Clinicopathological Study of Osteosarcoma Patients with Metachronous Metastatic Relapse.Journal of Cancer · 2019Article
- Manipulation of Glucose and Hydroperoxide Metabolism to Improve Radiation Response.Seminars in radiation oncology · 2019Review
- Proteasome Inhibitor MG132 Enhances Cisplatin-Induced Apoptosis in Osteosarcoma Cells and Inhibits Tumor Growth.Oncology research · 2018Article
- Auranofin radiosensitizes tumor cells through targeting thioredoxin reductase and resulting overproduction of reactive oxygen species.Oncotarget · 2017Article
- Selenoproteins and Metastasis.Advances in cancer research · 2017Review
- Article
- X-ray structures of thioredoxin and thioredoxin reductase from Entamoeba histolytica and prevailing hypothesis of the mechanism of Auranofin action.Journal of structural biology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS) accounts for 56% of malignant bone cancers in children and adolescents. Patients with localized disease rarely develop metastasis; however, pulmonary metastasis occurs in approximately 50% of patients and leads to a 5-year survival rate of only 10-20%. Therefore, identifying the genes and pathways involved in metastasis, as new therapeutic targets, is crucial to improve long-term survival of OS patients. Novel markers that define metastatic OS were identified using comparative transcriptomic analyses of two highly metastatic (C1 and C6) and two poorly metastatic clonal variants (C4 and C5) isolated from the metastatic OS cell line, KHOS. Using this approach, we determined that the metastatic phenotype correlated with overexpression of thioredoxin reductase 2 (TXNRD2) or vascular endothelial growth factor (VEGF). Validation in patient biopsies confirmed TXNRD2 and VEGF targets were highly expressed in 29-42% of metastatic OS patient biopsies, with no detectable expression in non-malignant bone or samples from OS patients with localised disease. Auranofin (AF) was used to selectively target and inhibit thioredoxin reductase (TrxR). At low doses, AF was able to inhibit TrxR activity without a significant effect on cell viability whereas at higher doses, AF could induce ROS-dependent apoptosis. AF treatment, in vivo, significantly reduced the development of pulmonary metastasis and we provide evidence that this effect may be due to an AF-dependent increase in cellular ROS. Thus, TXNRD2 may represent a novel druggable target that could be deployed to reduce the development of fatal pulmonary metastases in patients with OS.
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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.