ArticleCancer & metabolism2025
Glutathione peroxidase 4 (GPX4) and obesity interact to impact tumor progression and treatment response in triple negative breast cancer.
Article in Cancer & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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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
5 citing papers in PubMed.
- Celastrol at the obesity-cancer interface: critical appraisal of molecular mechanisms, preclinical evidence, and translational barriers.Molecular biology reports · 2026Review
- Breast cancer pathogenesis, diagnosis and treatment: a comprehensive review.Frontiers in oncology · 2026Review
- Programmed cell death in triple-negative breast cancer.Cellular & molecular biology letters · 2025Review
- Ferroptosis and Metabolic Dysregulation: Emerging Chemical Targets in Cancer and Infection.Molecules (Basel, Switzerland) · 2025Review
- Triple-negative breast cancer and ferroptosis: expression profiling of key regulatory genes.Archives of medical science : AMS · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
introductionTriple-negative breast cancer (TNBC), which tends to be more advanced when diagnosed and more aggressive than other breast cancer subtypes, is accelerated by obesity. Hypertrophic adipocytes and cancer cells exhibit increased oxidative stress and altered redox homeostasis, influencing therapeutic outcomes. Enzymes implicated in both redox regulation and TNBC include glutathione peroxidase 4 (GPX4; reduces lipid peroxides) and pyruvate carboxylase (PC; essential in oxidative stress protection). Using preclinical models, we characterized interactions between GPX4, PC, and oxidative stress in TNBC cells, and established effects of GPX4 suppression on TNBC progression. In TNBC cells, PC knockdown increased GPX4 expression, while GPX4 knockdown increased PC expression. GPX4 inhibition by erastin or RSL3 enhanced TNBC cell death in vitro, and antioxidants mitigated the cytotoxicity. In obese mice, GPX4 knockdown, versus scramble control: (i) reduced tumor burden following orthotopic transplantation of TNBC cells; and (ii) reduced lung metastasis following tail vein injection of TNBC cells in combination with chemotherapy (carboplatin) but not immunotherapy (anti-CTLA4 plus anti-PD1). We conclude that GPX4 and PC expression are inversely related in TNBC cells, and GPX4 and obesity interact to impact TNBC progression and treatment responses. Moreover, GPX4-mediated redox defense, alone or in combination with chemotherapy, is a targetable vulnerability for treating TNBC, including obesity-related TNBC. IMPLICATION: GPX4 suppression, alone or with current TNBC therapies, impacts outcomes in preclinical TNBC models with or without obesity and offers a new, plausible mechanistic target for TNBC 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.