ArticleMolecular cancer therapeutics2018
Metabolite Profiling Reveals the Glutathione Biosynthetic Pathway as a Therapeutic Target in Triple-Negative Breast Cancer.
Article in Molecular cancer therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Unraveling Biomarker Signatures in Triple-Negative Breast Cancer: A Systematic Review for Targeted Approaches.International journal of molecular sciences · 2024Pooled it
- Review
- The Landscape of Ferroptosis-Related Gene Signatures as Molecular Stratification in Triple-Negative Breast Cancer.Diagnostics (Basel, Switzerland) · 2026Article
- Mitochondrial Redox Vulnerabilities in Triple-Negative Breast Cancer: Integrative Perspectives and Emerging Therapeutic Strategies.Metabolites · 2026Review
- Metabolic Regulation of Ferroptosis in Breast Cancer.International journal of molecular sciences · 2025Review
- Metabolomics as a tool for understanding and treating triple-negative breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Ferroptosis in TNBC: interplay with tumor-infiltrating immune cells and therapeutic implications.Molecular and cellular biochemistry · 2025Review
- KDM4C inhibition blocks tumor growth in basal breast cancer by promoting cathepsin L-mediated histone H3 cleavage.Nature genetics · 2025Article
- Comprehensive analysis of the metabolomics and transcriptomics uncovers the dysregulated network and potential biomarkers of Triple Negative Breast Cancer.Journal of translational medicine · 2024Article
- Metabolic and Oxidative Stress Management Heterogeneity in a Panel of Breast Cancer Cell Lines.Metabolites · 2024Article
- Cellular Responses Induced by NCT-503 Treatment on Triple-Negative Breast Cancer Cell Lines: A Proteomics Approach.Biomedicines · 2024Article
- NRF2 activation by cysteine as a survival mechanism for triple-negative breast cancer cells.Oncogene · 2024Article
- Mechanism of ferroptosis in breast cancer and research progress of natural compounds regulating ferroptosis.Journal of cellular and molecular medicine · 2024Review
- Hinokitiol-iron complex is a ferroptosis inducer to inhibit triple-negative breast tumor growth.Cell & bioscience · 2023Article
- Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin.Molecules (Basel, Switzerland) · 2023Article
- Review
- Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer.Frontiers in immunology · 2023Article
- The AMPK-related kinase NUAK2 suppresses glutathione peroxidase 4 expression and promotes ferroptotic cell death in breast cancer cells.Cell death discovery · 2022Article
- Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies.Journal of hematology & oncology · 2022Review
- Impact of the PdInternational journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Cancer cells can exhibit altered dependency on specific metabolic pathways and targeting these dependencies is a promising therapeutic strategy. Triple-negative breast cancer (TNBC) is an aggressive and genomically heterogeneous subset of breast cancer that is resistant to existing targeted therapies. To identify metabolic pathway dependencies in TNBC, we first conducted mass spectrometry-based metabolomics of TNBC and control cells. Relative levels of intracellular metabolites distinguished TNBC from nontransformed breast epithelia and revealed two metabolic subtypes within TNBC that correlate with markers of basal-like versus non-basal-like status. Among the distinguishing metabolites, levels of the cellular redox buffer glutathione were lower in TNBC cell lines compared to controls and markedly lower in non-basal-like TNBC. Significantly, these cell lines showed enhanced sensitivity to pharmacologic inhibition of glutathione biosynthesis that was rescued by N-acetylcysteine, demonstrating a dependence on glutathione production to suppress ROS and support tumor cell survival. Consistent with this, patients whose tumors express elevated levels of γ-glutamylcysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, had significantly poorer survival. We find, further, that agents that limit the availability of glutathione precursors enhance both glutathione depletion and TNBC cell killing by γ-glutamylcysteine ligase inhibitors
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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.