Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: 235, P. 231 - 247
Published: May 1, 2025
Language: Английский
Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 334 - 334
Published: Feb. 26, 2025
In recent years, ferroptosis, as an emerging modality of programmed cell death, has captured significant attention within the scientific community. This comprehensive review meticulously canvasses pertinent literature past few spanning multiple facets. It delves into intricate mechanisms underpinning tracks evolution its inducers and inhibitors, dissects roles in a diverse array diseases, well resultant therapeutic implications. A profound exploration is conducted functional ferroptosis-related molecules, intracellular pathways, metabolic cascades, signaling transduction routes. Novel ferroptosis inhibitors are introduced detail, covering their design blueprints, synthetic methodologies, bioactivity profiles. Moreover, exhaustive account provided regarding involvement malignancies, neurodegenerative disorders, cardiovascular ailments, other pathologies. By highlighting pivotal status potential regimens various this aspires to furnish thorough reference framework for future investigations clinical translations domain.
Language: Английский
Citations
3
Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)
Published: Nov. 30, 2024
Abstract Ferroptosis is a type of regulated cell death characterized by its non-apoptotic, iron-dependent and oxidative nature. Since discovery in 2012, extensive research has demonstrated pivotal roles tumorigenesis, metastasis cancer therapy. The tumor microenvironment (TME) complex ecosystem comprising cells, non-cancer extracellular matrix, metabolites cytokines. Recent studies have underscored new paradigm which cells the TME, such as immune stromal also play significant regulating progression therapeutic resistance typically through complicated crosstalk with cells. Notably, this TME were partially mediated ferrotopsis-related mechanisms. This review provides comprehensive systematic summary current findings concerning ferroptosis how ferroptosis-mediated reprogramming impacts progression. Additionally, outlines various ferroptosis-related strategies aimed at targeting TME.
Language: Английский
Citations
10
Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 958 - 958
Published: April 14, 2025
Background/Objectives: PARP inhibitors (PARPi) are pivotal to treating homologous recombination repair-deficient (HRD) cancers, particularly BRCA1/2-mutated ovarian and breast cancers. However, most cancers harbor wild-type (WT) BRCA1/2, limiting PARPi eligibility. This study aims identify an approved drug that could induce a BRCAness phenotype, thereby sensitizing WT BRCA PARPi. Methods: Ovarian cancer cell lines with BRCA1/2 were treated ivosidenib. HR repair efficiency was assessed via RAD51 foci formation reporter assays. Synthetic lethality evaluated using viability colony Mechanistic studies included RNA-binding protein pulldown, co-immunoprecipitation, functional analyses of DNA pathways. YTHDC2′s role in investigated through siRNA knockdown rescue experiments. Results: Ivosidenib significantly reduced sensitized cells PARPi, inducing synthetic lethality. Mechanistically, ivosidenib directly bound YTHDC2, m6A reader critical for HR. interaction disrupted ability promote double-strand break HR, evidenced by impaired recruitment proteins (e.g., BRCA1, RAD51) accumulation damage (γH2AX foci). YTHDC2 phenocopied effects, while overexpression rescued defects. Conclusions: induces targeting suppressing enhancing sensitivity. uncovers novel, metabolism-independent mechanism ivosidenib, repositioning it as therapeutic agent HRD tumors. These findings propose strategy expand eligibility addressing unmet need oncology.
Language: Английский
Citations
0
European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)
Published: April 17, 2025
Understanding the core principles of ovarian cancer has been significantly improved through exploration Ferroptosis, a type cell death triggered by iron that leads to an increase in lipid peroxides. Current research shed light on critical functions non-coding RNAs, such as circRNAs, lncRNAs, and miRNAs, regulating ferroptosis cancer. The aim this paper is comprehensively analyze how ncRNAs influence development cells. In-depth undertaken understand intricate ways which regulate essential elements ferroptosis, including management peroxidation levels. We also investigate their significant involvement progression cellular demise. It should be emphasized can impact synthesis crucial proteins, GPX4, key contributor defense against oxidation, ACSL4, involved formation. In addition, we examine correlation between well-known pathways associated with oxidative stress death. consequences these discoveries are noteworthy, since focusing particular could potentially render cells more vulnerable effectively combating drug resistance problems. This discussion highlights growing significance governing potential useful biomarkers treatment targets for intend promote additional into controlling based current findings, ultimate goal informing targeted therapeutic strategies improving long-term outcomes individuals suffering from OC.
Language: Английский
Citations
0
Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)
Published: April 19, 2025
Abstract As an important protein post-translational modification process, ubiquitination plays indispensable role in the regulation of gastric cancer (GC) occurrence and development. And recent studies have demonstrated that this is closely related to regulated cell death. This suggests our therapeutic approach inhibit malignant progression GC by regulating intracellular death mode through becomes possible. Although has been well described some tumorigenesis, its potential specific mechanisms are still unknown. In present study, we identified RNF128, E3 ubiquitin ligase with a RING structural domain, whose expression was significantly increased GC. In-depth showed knockdown RNF128 inhibited proliferation autophagic flux lipid peroxidation production, hypothesized autophagy-dependent ferroptosis might be main mediated RNF128. Mechanistically, directly binds ubiquitinates degradation Beclin1 PA domain inhibits Beclin1/solute transport family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4) axis. Taken together, study reports for first time acts as tumor promoter GCs targeting Beclin1. These data provide new insights into activation expected strategy molecular therapy clinical patients.
Language: Английский
Citations
0
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16
Published: April 24, 2025
Ovarian cancer, a gynecologic malignancy with high mortality rates, faces persistent therapeutic challenges due to acquired resistance and frequent recurrence conventional therapies. While poly (ADP-ribose) polymerase (PARP) inhibitors have primarily transformed clinical outcomes through the synthetic lethality mechanism, their long-term efficacy remains constrained by resistance. Ferroptosis, novel programmed cell death modality characterized iron-dependent lipid peroxidation, has emerged as promising frontier in oncology. This review is first summarize mechanisms of action associated both ferroptosis PARP ovarian cancer.
Language: Английский
Citations
0
Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: 235, P. 231 - 247
Published: May 1, 2025
Language: Английский
Citations
0