Cuproptosis: unveiling a new frontier in cancer biology and therapeutics

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 1, 2024

Copper plays vital roles in numerous cellular processes and its imbalance can lead to oxidative stress dysfunction. Recent research has unveiled a unique form of copper-induced cell death, termed cuproptosis, which differs from known death mechanisms. This process involves the interaction copper with lipoylated tricarboxylic acid cycle enzymes, causing protein aggregation death. Recently, growing number studies have explored link between cuproptosis cancer development. review comprehensively examines systemic metabolism copper, including tumor-related signaling pathways influenced by copper. It delves into discovery mechanisms connection various cancers. Additionally, suggests potential treatments using ionophores that induce combination small molecule drugs, for precision therapy specific types.

Language: Английский

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Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(5), P. 4646 - 4687

Published: May 13, 2024

This review systematizes information about the metabolic features of breast cancer directly related to oxidative stress. It has been shown those redox changes occur at all levels and affect many regulatory systems in human body. The biochemical processes occurring are described, ranging from nonspecific, first glance, strictly hormone-induced reactions, genetic epigenetic regulation, which allows for a broader deeper understanding principles oncogenesis, as well maintaining viability cells mammary gland. Specific pathways activation stress have studied response overproduction hormones estrogens, specific ways reduce its negative impact described. diversity participants that trigger reactions different sides is considered more fully: glycolytic activity cancer, nature consumption amino acids metals. role metals discussed detail. They can act both co-factors direct stress, since they either mechanism lipid peroxidation or capable activating signaling tumorigenesis. Special attention paid regulation tumors. A complex cascade mechanisms explained, made it possible reconsider existing opinion triggers launching oncological process, survival their ability localize.

Language: Английский

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Design and synthesis of antiproliferative 2-oxoindolin-3-ylidenes incorporating urea function with potential VEGFR-2 inhibitory properties

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 3, 2025

Language: Английский

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Modifying metabolic and immune hallmarks of cancer by a copper complex

Science China Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

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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Identification and Immunological Characterization of Cuproptosis Related Genes in Preeclampsia Using Bioinformatics Analysis and Machine Learning

Journal of Clinical Hypertension, Journal Year: 2025, Volume and Issue: 27(1)

Published: Jan. 1, 2025

Preeclampsia (PE) is a pregnancy-specific disorder characterized by an unclearly understood pathogenesis and poses great threat to maternal fetal safety. Cuproptosis, novel form of cellular death, has been implicated in the advancement various diseases. However, role cuproptosis immune-related genes PE unclear. The current study aims elucidate gene expression matrix immune infiltration patterns cuproptosis-related (CRGs) context PE. GSE98224 dataset was obtained from Gene Expression Omnibus (GEO) database utilized as internal training set. Based on dataset, we explored differentially expressed related (DECRGs) immunological composition. We identified 10 DECRGs conducted Ontology (GO) function, Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses, protein-protein interaction (PPI) network. Furthermore, patients with were categorized into two distinct clusters, investigation examine status cell infiltration. Additionally, application Weighted Co-expression Network Analysis (WGCNA) differentiate modules consisting co-expressed conduct clustering analysis. intersecting differently clusters. most precise forecasting model chosen evaluating effectiveness four machine learning models. ResNet established score hub genes. prediction accuracy assessed receiver operating characteristic (ROC) curves external dataset. successfully five key DECREGs pathological clusters PE, each profiles biological characteristics. Subsequently, RF deemed optimal for identification large area under curve (AUC = 0.733). that ranked highest considered be predictor calibration demonstrated high level aligning predicted outcomes actual outcomes. validate using ROC 0.82). Cuproptosis may play important present elucidated GSTA4, KCNK5, APLNR, IKZF2, CAP2 potential markers cuproptosis-associated are significant initiation development cuproptosis-induced

Language: Английский

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Copper in cancer: friend or foe? Metabolism, dysregulation, and therapeutic opportunities

Cancer Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Abstract Copper, one of the essential nutrients for human body, acts as an electron relay in multiple pathways due to its redox properties. Both deficiencies and excesses copper lead cellular fragility. Therefore, it can manifest pro‐ anti‐cancer properties tumors. is crucial clarify activity within cell. We have thoughtfully summarized metabolic activities from a macro micro perspective. Cuproptosis, well other forms cell death, directly or indirectly interfered with by Cu 2+ , causing cancer death. Meanwhile, we did pan‐cancer analysis cuproptosis‐related genes further roles these genes. In addition, has been found be involved metastasis cells. Given complexity copper's role, are compelled ask: friend foe? Up now, used various clinical applications, including protocols measurement concentration bioimaging radioactive 64 Cu. But therapeutically still continuation old medicine, new possibilities need explored, such use nanomaterials. Some studies also shown that considerable interventional power cancers, which provides great applications potential therapy specific types. This paper reviews dual played cuproptosis perspectives oxidative stress, tumor metastasis, points out value application types, summarizes testing imaging perspective current feasible options drugs, emphasizes prospects nano‐copper.

Language: Английский

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Big data analysis and machine learning of the role of cuproptosis-related long non-coding RNAs (CuLncs) in the prognosis and immune landscape of ovarian cancer

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 25, 2025

Ovarian cancer (OC) is a severe malignant tumor with significant threat to women's health, characterized by high mortality rate and poor prognosis despite conventional treatments such as cytoreductive surgery platinum-based chemotherapy. Cuproptosis, novel form of cell death triggered copper ion accumulation, has shown potential in therapy, particularly through the involvement CuLncs. This study aims identify risk signatures associated CuLncs OC, construct prognostic model, explore therapeutic drugs impact on OC behavior. We analyzed ovarian data (TCGA-OV) from TCGA database, including transcriptomic clinical 376 patients. Using Pearson correlation LASSO regression, we identified 8 signature model. Patients were categorized into high- low-risk groups based their scores. performed survival analysis, model validation, drug sensitivity vitro experiments assess model's performance functional key proliferation, invasion, migration. The demonstrated predictive power, an area under curve (AUC) 0.702 for 1-year, 0.640 3-year, 0.618 5-year survival, outperforming pathological features stage grade. High-risk patients exhibited higher Tumor Immune Dysfunction Exclusion (TIDE) scores, indicating stronger immune evasion ability. Drugs JQ12, PD-0325901, sorafenib showed reduced IC50 values high-risk group, suggesting benefits. In revealed that knockdown LINC01956, CuLnc signature, significantly inhibited migration cells (P<0.05). Our explored targets OC. findings highlight importance response, providing new insights future research applications.

Language: Английский

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Common Regulatory Mechanisms Mediated by Cuproptosis Genes in Inflammatory Bowel Disease and Major Depressive Disorder

Genes, Journal Year: 2025, Volume and Issue: 16(3), P. 339 - 339

Published: March 14, 2025

Background: The prevalence of major depressive disorder (MDD) among patients with inflammatory bowel disease (IBD) is significantly higher compared to the general population, suggesting a potential link between their pathogeneses. Cuproptosis, defined as cell death caused by intracellular copper accumulation, has not been thoroughly investigated in context IBD and MDD. This study aims uncover molecular mechanisms cuproptosis-related genes (CRGs) both conditions explore novel therapeutic strategies modulation CRGs. Methods: In this study, we identified differentially expressed CRGs normal samples. We calculated correlation immune infiltrations across various tissues. Four machine learning algorithms were employed identify key associated Additionally, drug sensitivity, docking, dynamics simulations conducted predict drugs for Results: DLD, DLAT, DLST, PDHB, DBT common DE-CRGs, LIAS, SLC31A1, SCO2, CDKN2A Consequently, DLD was recognized shared biomarker diseases. A total 37 Based on docking simulation analyses, barasertib NTP-TAE684, which target predicted be most effective compounds. Conclusions: These findings have substantially enhanced our understanding similarities differences regulatory within brain–gut axis Key biomarkers identified, effectively

Language: Английский

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Integrated bulk and single-cell transcriptomic analysis unveiled a novel cuproptosis-related lipid metabolism gene molecular pattern and a risk index for predicting prognosis and antitumor drug sensitivity in breast cancer

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 14, 2025

Breast cancer is the second most prevalent malignant tumor worldwide and highly heterogeneous. Cuproptosis, a newly identified form of cell death, intimately connected to lipid metabolism. This study investigated breast heterogeneity through lens cuproptosis-related metabolism genes (CLMGs), with goal predicting patient prognosis, immunotherapy efficacy, sensitivity anticancer drugs. By utilizing transcriptomic data from The Cancer Genome Atlas (TCGA) for cancer, we 682 CLMGs applied nonnegative matrix factorization (NMF) method categorize patients into four distinct clusters: cluster 1, ''immune-cold stroma-poor''; 2, ''immune-infiltrated''; 3, ''stroma-rich''; 4, ''moderate infiltration''. We subsequently developed risk model based on that incorporates ACSL1, ATP2B4, ATP7B, ENPP6, HSPH1, PIP4K2C, SRD5A3, ULBP1. demonstrated excellent prognostic predictive performance in both internal (testing entire sets) external (GSE20685 Kaplan–Meier Plotter validation sets. High-risk presented lower expression levels immune checkpoint-related immunophenoscores (IPSs), whereas low-risk higher CD8+ T-cell infiltration IPSs. Furthermore, index was positively correlated stemness could predict also confirmed SRD5A3 expressed participated promoting proliferation migration cells. In conclusion, results this provide new insights strategies assessing prognosis implementing precision treatment CLMGs.

Language: Английский

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