Iron-Dependent Cell Death: Exploring Ferroptosis as a Unique Target in Triple-Negative Breast Cancer Management

Cancer Management and Research, Journal Year: 2025, Volume and Issue: Volume 17, P. 625 - 637

Published: March 1, 2025

Triple-negative breast cancer (TNBC) is characterized by aggressive behavior, high metastatic potential, and frequent relapses, presenting significant treatment challenges. Ferroptosis, a unique form of programmed cell death marked iron-dependent lipid peroxidation, has emerged as crucial factor in biology. Recent studies indicate that TNBC cells possess distinct metabolic profile linked to iron glutathione, which may render them more susceptible ferroptosis than other subtypes. Moreover, plays role the interactions between immune tumor cells, suggesting its potential modulate microenvironment influence response against TNBC.Evidence reveals not only affects viability but also alters promoting release damage-associated molecular patterns (DAMPs), can recruit site. Specific ferroptosis-related genes biomarkers, such ACSL4 GPX4, demonstrate altered expression tissues, offering promising avenues for diagnostic prognostic applications. Furthermore, preclinical models, induction been shown enhance efficacy existing therapies, indicating synergistic effect could be harnessed therapeutic benefit. The compelling link underscores novel target. Future research should focus on developing strategies exploit conjunction with traditional including identification natural compounds efficacious inducers personalized regimens. This review elucidates multifaceted implications TNBC, providing valuable insights improving both diagnosis this formidable subtype.

Language: Английский

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The role of ferroptosis in breast cancer: tumor progression, immune microenvironment interactions and therapeutic interventions

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: 996, P. 177561 - 177561

Published: March 28, 2025

Language: Английский

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The Mutual Regulatory Role of Ferroptosis and Immunotherapy in Anti-tumor Therapy

APOPTOSIS, Journal Year: 2024, Volume and Issue: unknown

Published: June 9, 2024

Abstract Ferroptosis is a form of cell death that triggered by the presence ferrous ions and characterized lipid peroxidation induced these ions. The mechanism exhibits distinct morphological characteristics compared to apoptosis, autophagy, necrosis. A notable aspect ferroptosis its ability inhibit uncontrolled tumor replication immortalization, especially in malignant, drug-resistant, metastatic tumors. Additionally, immunotherapy, novel therapeutic approach for tumors, has been found have reciprocal regulatory relationship with context anti-tumor therapy. comprehensive analysis immunotherapy therapy presented this paper, highlighting potential mutual adjuvant effects. Specifically, we discuss mechanisms underlying emphasizing their improve immune microenvironment enhance immunotherapeutic Furthermore, investigate how factors may increase sensitivity cells ferroptosis. We aim provide prospective view promising value combined anticancer elucidating network between each. Graphical involves intricate crosstalk cells. Through MHC recognition, CD8 + T activate JAK1/STAT1 pathway cells, impairing function System Xc reducing GSH GPX4 expression promote activation STAT1-IRF1-ACSL4 could also blockade antioxidant induces ferroptosis, released DAMPs DCs maturation through cGAMP-STING-TBK1 pathway, leading antigen presentation activates release M1-type polarization macrophages, which exerts an effect. effects be enhanced blocking inhibitory checkpoints such as PD-1, PD-L1, CTLA4, LAG3. Abbreviations: ACSL4, acyl-CoA synthetase long-chain family member 4; BH4, tetrahydrobiopterin; cGAMP, cyclic GMP-AMP; cytotoxic lymphocyte-associated antigen-4; DCs, dendritic cells; DHFR, dihydrofolate reductase; DHODH, dihydroorotate dehydrogenase; GPX4, glutathione peroxidase GSH, glutathione; HIF-1α, Hypoxia-Inducible Factor-1α;IFN-γ, interferon-γ; IRF1, interferon factor 1;IRP1, iron protein 1; JAK 1, janus kinase; LAG3, lymphocyte gene 3; MHC, major histocompatibility complex; NRF2, nuclear erythroid-2-related 2; programmed -1; ligand PUFA, polyunsaturated fatty acid; ROS, reative oxygen species; STAT1, signal transducer activator transcription STING, stimulator genes; TBK1, TANK-binding kinase 1 TLR2, toll-like receptor 2. This diagram was drawn Figdraw ( www.figdraw.com ).

Language: Английский

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Targeting the initiator to activate both ferroptosis and cuproptosis for breast cancer treatment: progress and possibility for clinical application

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

Breast cancer is the most commonly diagnosed worldwide. Metal metabolism pivotal for regulating cell fate and drug sensitivity in breast cancer. Iron copper are essential metal ions critical maintaining cellular function. The accumulation of iron triggers distinct death pathways, known as ferroptosis cuproptosis, respectively. Ferroptosis characterized by iron-dependent lipid peroxidation, while cuproptosis involves copper-induced oxidative stress. They increasingly recognized promising targets development anticancer drugs. Recently, compelling evidence demonstrated that interplay between plays a crucial role progression. This review elucidates converging pathways Moreover, we examined value genes associated with clinical diagnosis treatment cancer, mainly outlining potential co-targeting approach. Lastly, delve into current challenges limitations this strategy. In general, offers an overview interaction offering valuable perspectives further research treatment.

Language: Английский

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Cancer-associated fibroblasts promote doxorubicin resistance in triple-negative breast cancer through enhancing ZFP64 histone lactylation to regulate ferroptosis

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 28, 2025

Cancer-associated fibroblasts (CAFs) have been identified to drive chemotherapy resistance in triple-negative breast cancer (TNBC). This study evaluated the functions of CAFs-mediated suppressive ferroptosis doxorubicin (DOX) TNBC and its detailed molecular mechanisms. cell lines were co-cultured with CAFs isolated from DOX-sensitive (CAF/S) or DOX-resistant (CAF/R) tissues. Cell viability death assessed by counting Kit-8 (CCK-8) propidium iodide (PI) staining. Ferroptosis was detection Fe2+, malondialdehyde (MDA), glutathione (GSH), lipid reactive oxygen species (ROS) levels. Histone lactylation determined lactate production, pan-Kla H3K18la expression. Molecular mechanism chromatin immunoprecipitation (ChIP) dual luciferase reporter system. Molecule protein expression detected quantitative Real-Time PCR (RT-qPCR), Western blotting, immunofluorescence immunohistochemical cells injected into mammary fat pad nude mice investigate DOX sensitivity vivo. CAFs-derived repressed confer DOX. Moreover, zinc finger 64 (ZFP64) elevated associated high histone level. facilitated enhance ZFP64 expression, which triggered inhibition resistance. In addition, bound promoters GTP cyclohydrolase-1 (GCH1) ferritin heavy chain 1 (FTH1), thereby promoting their Rescue experiments indicated that silencing-induced could be counteracted GCH1 FTH1 overexpression. acted as a inhibitor cause via lactylation-mediated up-regulation subsequent promotion GCH1-induced peroxidation FTH1-induced intracellular Fe2+ consumption.

Language: Английский

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