ReviewInternational journal of molecular sciences2025
Emerging Therapeutic Strategies Targeting GPX4-Mediated Ferroptosis in Head and Neck Cancer.
Review in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Ferroptosis as a Translational Axis in Small Cell Lung Cancer: A Systematic Review of Redox Pathways and Precision Oncology Prospects.Oncology research · 2026Pooled it
- Ferroptosis and tumor microenvironment: orchestrating therapy resistance, immune evasion, and metastatic events.Medical oncology (Northwood, London, England) · 2026Review
- Molecular Mechanisms of Obesity-Associated Oxidative Stress and Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- The Dynamic Alliance of p53 and Metabolism in the Tumor Microenvironment Shapes Tumor Evolution.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Review
- GSH-Related Enzymes GPx4, Chac1, and GSTs and Redox Regulation of Ferroptosis in Cancer.International journal of molecular sciences · 2026Review
- GPX4 in the Tumor Microenvironment: Not Just Inhibiting Ferroptosis, but Immuno-Metabolic Regulation.Biomolecules · 2026Review
- Potential diagnostic, prognostic, and therapeutic implications of ferroptosis in myelodysplastic syndromes.Discover oncology · 2026Review
- The Interaction Between Iron and Selenium Affects Ferroptosis in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Interconnected cell death pathways: central mechanisms and therapeutic targets in impaired follicular development of polycystic ovary syndrome.Journal of ovarian research · 2026Review
- The Role of Se-Containing Glutathione Peroxidases and Thioredoxin Reductases in Oncogenesis: Expression Paradoxes and Therapeutic Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- HDAC inhibitors as ferroptosis sensitizers in cancer: Epigenetic regulation of redox balance and iron metabolism.EXCLI journal · 2026Review
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
- Iron homeostasis and macrophage polarization in oral squamous cell carcinoma: mechanisms and therapeutic perspectives.Frontiers in immunology · 2026Review
- The Redox-Adhesion-Exosome (RAX) Hub in Cancer: Lipid Peroxidation-Driven EMT Plasticity and Ferroptosis Defense with HNE/MDA Signaling and Lipidomic Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- Metabolic cell deaths in head and neck cancer: mechanisms, therapeutic potential, and challenges.Annals of medicine · 2025Review
- Targeting Ferroptosis in Nasopharyngeal Carcinoma: Mechanisms, Resistance, and Precision Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Ferroptosis and head and neck cancer: Mechanisms and therapeutic perspectives (Review).International journal of molecular medicine · 2025Review
- Review
- Harnessing the gut microbiome to modulate ferroptosis: a metabolic strategy for the treatment of digestive tract cancers.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Ferroptosis, a regulated form of iron-dependent lipid peroxidation-induced cell death, has emerged as a compelling therapeutic strategy to overcome treatment resistance in head and neck cancer (HNC). Glutathione peroxidase 4 (GPX4), a selenoenzyme responsible for detoxifying phospholipid hydroperoxides, plays a central role in blocking ferroptosis and is frequently upregulated in therapy-resistant HNC subtypes. In this review, we examine the multifaceted regulation of GPX4 expression and function, including transcriptional, post-transcriptional, epigenetic, and proteostatic mechanisms. We explore how GPX4 suppression through pharmacologic inhibitors (e.g., RSL3, withaferin A, statins), metabolic stress, or combined therapies (e.g., radiotherapy, EGFR inhibitors, immunotherapy) induces ferroptosis and resensitizes resistant tumors. We also summarize emerging biomarkers, including GPX4, ACSL4, SLC7A11, and NCOA4, that predict ferroptosis sensitivity and may guide patient selection for ferroptosis-targeted therapies. Single-cell and spatial transcriptomics reveal significant intratumoral heterogeneity in ferroptosis susceptibility, underscoring the need for precision approaches. Despite promising preclinical data, challenges such as drug delivery, toxicity, and resistance mechanisms remain. Nevertheless, the ferroptosis-GPX4 axis represents a unique vulnerability in HNC that can be therapeutically exploited. Integrating ferroptosis modulation into personalized oncology may transform outcomes for patients with refractory disease.
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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.