ArticleOncotarget2016
NRF2 and glutathione are key resistance mediators to temozolomide in glioma and melanoma cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 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
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- The dual role of Nrf2 in melanoma: a systematic review.BMC molecular and cell biology · 2023Pooled it
- Succinate Dehydrogenase Subunit D as a Redox-Responsive Mitochondrial Component Linked to Aquaporin-Associated Hydrogen Peroxide Signaling in Glioblastoma Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Brain Cancer: Molecular Alterations and Emerging Trends in Neuropharmacology.International journal of molecular sciences · 2026Review
- Overcoming Chemoresistance in Glioblastoma: Mechanisms, Therapeutic Strategies, and Functional Precision Medicine.International journal of molecular sciences · 2026Review
- Targeting metabolic mechanisms to overcome temozolomide resistance in glioblastoma.Discover oncology · 2026Review
- Systemic cyst(e)inase administration induces ferroptosis and synergizes with temozolomide in glioblastoma.iScience · 2026Article
- From metabolism to genome integrity: NRF2 as a key mediator of cancer therapy response.Frontiers in cell and developmental biology · 2026Review
- The evolution of chemotherapy in brain tumors: from historical milestones to precision medicine in glioblastoma.Exploration of targeted anti-tumor therapy · 2026Review
- Convergent adaptive architectures linking chemoresistance and radioresistance in chemoradiotherapy: a systems-level perspective.Frontiers in oncology · 2026Review
- Analysis of metabolic rewiring in MDR1-overexpressing drug-resistant glioblastoma.Frontiers in pharmacology · 2026Article
- Caspase-8 expression and its Src dependent phosphorylation on Tyrosine 380 triggers NRF2 signaling activation in glioblastoma.Cell death and differentiation · 2025Article
- Small molecular weight polyfluoroalkyl phosphonates induce ROS-mediated cytotoxicity in glioblastoma cells: a molecular mechanism study.Scientific reports · 2025Article
- Harnessing ferroptosis to transform glioblastoma therapy and surmount treatment resistance.Cell death discovery · 2025Review
- COX-2 Inhibition in Glioblastoma Cells Counteracts Resistance to Temozolomide by Inducing Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes.Translational oncology · 2025Review
- Inhibition of Thioredoxin-Reductase by Auranofin as a Pro-Oxidant Anticancer Strategy for Glioblastoma: In Vitro and In Vivo Studies.International journal of molecular sciences · 2025Review
- "Effects of Redox Status on Immediate Hypericin-Mediated Photodynamic Therapy in Human Glioblastoma T98G Cell Line".ACS omega · 2025Article
- State-of-the-art photodynamic therapy for malignant gliomas: innovations in photosensitizers and combined therapeutic approaches.Exploration of targeted anti-tumor therapy · 2025Review
- Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Proteomics Studies on Extracellular Vesicles Derived from Glioblastoma: Where Do We Stand?International journal of molecular sciences · 2024Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer is a leading cause of death worldwide, and while great advances have been made particularly in chemotherapy, many types of cancer still present a dismal prognosis. In the case of glioma, temozolomide (TMZ) is the main option for treatment, but it has limited success due to drug resistance. While this resistance is usually associated to DNA repair mechanisms, in this work we demonstrate that oxidative stress plays an important role. We showed that upon TMZ treatment there is an induction of the nuclear factor erythroid 2-related factor 2 (NRF2), which is the main antioxidant transcription factor regulator in human cells. This is accompanied by an enhancement of glutathione (GSH) concentration in the tumor cells. The effectiveness of this pathway was proven by silencing NFR2, which greatly enhanced cell death upon TMZ treatment both in vitro and in vivo. Also, higher DNA damage and induced cell death was observed by combining BSO - a GSH inhibitor - with TMZ. Similar effects were also observed using in vitro and in vivo models of melanoma, thus possibly indicating that GSH has a decisive role in TMZ resistance in a wider range of tumors. Thus, a combined regimen of BSO and TMZ configures an interesting therapeutic alternative for fighting both glioma and melanoma.
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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.