Cuproptosis: A novel therapeutic target for overcoming cancer drug resistance

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 72, P. 101018 - 101018

Published: Nov. 11, 2023

Cuproptosis is a newly identified form of cell death driven by copper. Recently, the role copper and triggered in pathogenesis cancers have attracted attentions. has garnered enormous interest cancer research communities because its great potential for therapy. Copper-based treatment exerts an inhibiting tumor growth may open door chemotherapy-insensitive tumors. In this review, we provide critical analysis on homeostasis dysregulation development progression cancers. Then core molecular mechanisms cuproptosis discussed, followed summarizing current understanding copper-based agents (copper chelators, ionophores, complexes-based dynamic therapy) treatment. Additionally, summarize emerging data ionophores to subdue chemotherapy resistance different types We also review small-molecule compounds nanoparticles (NPs) that kill cells inducing cuproptosis, which will shed new light anticancer drugs through future. Finally, important concepts pressing questions future should be focused were discussed. This article suggests targeting could novel antitumor therapy strategy overcome drug resistance.

Language: Английский

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Copper homeostasis and cuproptosis in cancer immunity and therapy

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 211 - 227

Published: Sept. 16, 2023

Summary Copper is an essential nutrient for maintaining enzyme activity and transcription factor function. Excess copper results in the aggregation of lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), which correlates to mitochondrial tricarboxylic acid (TCA) cycle, resulting proteotoxic stress eliciting a novel cell death modality: cuproptosis. Cuproptosis exerts indispensable role cancer progression, considered promising strategy therapy. Cancer immunotherapy has gained extensive attention owing breakthroughs immune checkpoint blockade; furthermore, cuproptosis strongly connected modulation antitumor immunity. Thus, thorough recognition concerning mechanisms involved metabolism may facilitate improvement management. This review outlines cellular molecular characteristics links regulated modality with human cancers. We also current knowledge on complex effects immunity response. Furthermore, potential agents that elicit pathways are summarized. Lastly, we discuss influence induction tumor microenvironment as well challenges adding regulators therapeutic strategies beyond traditional

Language: Английский

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Unveiling the promising anticancer effect of copper-based compounds: a comprehensive review

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(4)

Published: April 25, 2024

Abstract Copper is a necessary micronutrient for maintaining the well-being of human body. The biological activity organic ligands, especially their anticancer activity, often enhanced when they coordinate with copper(I) and (II) ions. its compounds are capable inducing tumor cell death through various mechanisms action, including activation apoptosis signaling pathways by reactive oxygen species (ROS), inhibition angiogenesis, induction cuproptosis, paraptosis. Some copper complexes currently being evaluated in clinical trials ability to map hypoxia cancers, locally advanced rectal cancer bulky tumors. Several studies have shown that nanoparticles can be used as effective agents chemodynamic therapy, phototherapy, hyperthermia, immunotherapy. Despite promising copper-based compounds, use subject certain limitations. Elevated concentrations may promote growth, metastasis affecting cellular processes.

Language: Английский

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Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Aug. 16, 2024

Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and loss iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress triggering death. Recently, has garnered significant interest tumor research due to its potential as crucial therapeutic strategy against cancer. In this review, we summarized cellular molecular mechanisms relationship other types Additionally, reviewed current drugs or strategies available induce cells, including Cu ionophores, small compounds, nanomedicine. Furthermore, targeted metabolism specific regulatory genes cancer therapy enhance sensitivity cuproptosis. Finally, discussed feasibility targeting overcome chemotherapy immunotherapy resistance suggested future directions. This study that could open new avenues for developing therapy.

Language: Английский

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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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Progress and Challenges in Tumor Ferroptosis Treatment Strategies: A Comprehensive Review of Metal Complexes and Nanomedicine

Small, Journal Year: 2024, Volume and Issue: 20(25)

Published: Jan. 14, 2024

Abstract Ferroptosis is a new form of regulated cell death featuring iron‐dependent lipid peroxides accumulation to kill tumor cells. A growing body evidence has shown the potential ferroptosis‐based cancer therapy in eradicating refractory malignancies that are resistant apoptosis‐based conventional therapies. In recent years, studies have reported number ferroptosis inducers can increase vulnerability cells by regulating ferroptosis‐related signaling pathways. Encouraged rapid development ferroptosis‐driven therapies, interdisciplinary fields combine ferroptosis, pharmaceutical chemistry, and nanotechnology focused. First, prerequisites metabolic pathways for briefly introduced. Then, detail emerging designed boost ferroptosis‐induced therapy, including metal complexes, metal‐based nanoparticles, metal‐free nanoparticles summarized. Subsequently, application synergistic strategies with apoptosis other emphasis on use both cuproptosis induce redox dysregulation intracellular bimetallic copper/iron metabolism disorders during treatment discussed. Finally, challenges associated clinical translation future directions potentiating therapies highlighted.

Language: Английский

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N/O co-doping porous biomass carbon constructed electrochemical sensor for universal and sensitive detection to mycotoxins

Food Chemistry, Journal Year: 2025, Volume and Issue: 475, P. 143397 - 143397

Published: Feb. 12, 2025

Language: Английский

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Cuproptosis‐Inducible Chemotherapeutic/Cascade Catalytic Reactor System for Combating with Breast Cancer

Small, Journal Year: 2023, Volume and Issue: 19(35)

Published: May 10, 2023

Cascade hydroxyl radical generating hydrogel reactor structures including a chemotherapeutic agent are invented for multiple treatment of breast cancer. Glucose oxidase (GOx) and cupric sulfate (Cu) introduced transforming accumulated glucose (in cancer cells) to radicals starvation/chemodynamic therapy. Cu may also suppress cell growth via cuproptosis-mediated death. Berberine hydrochloride (BER) is engaged as in the combining with starvation/chemodynamic/cuproptosis therapeutic modalities. Moreover, participated gel crosslinker by coordinating catechol groups hyaluronic acid-dopamine (HD) polymer. Controlling viscoelasticity can extend retention time following local injection provide sustained drug release patterns. Low biodegradation rate designed HD/BER/GOx/Cu reduce dosing frequency therapy avoid invasiveness-related inconveniences. Especially, it anticipated that system be applied reducing size prior surgery well tumor suppression clinical application.

Language: Английский

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Bimetallic Ions Functionalized Metal–Organic‐Framework Nanozyme for Tumor Microenvironment Regulating and Enhanced Photodynamic Therapy for Hypoxic Tumor

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(26)

Published: May 18, 2023

Photodynamic therapy (PDT), as a light irradiation inducing reactive oxygen species (ROS) generation for cancer treatment, offers facile and promising solutions with respect to spatiotemporal control of ROS generation, minimizes the systemic toxicity side effects highly precise tumor therapy. However, PDT efficiency is often severely compromised by complex microenvironment (TME), such hypoxic condition overexpressed antioxidants. Here, first time, bimetallic ion-modified metal-organic framework nanozyme (Zr4+ -MOF-Ru3+ /Pt4+ -Ce6@HA, ZMRPC@HA) designed. ZMRPC@HA catalase (CAT) glutathione oxidase (GSHOx) mimetic activities, can efficiently regulate TME O2 deplete GSH synergistically enhancing long-term efficacy toward tumor. The in vitro cell inhibition vivo on xenograft evaluations demonstrate strategy using successfully inhibit differentiation proliferation cells under 660 nm laser deep tissues. These findings open new avenue design multimetallic ions functionalized MOF-based nanozymes multienzyme activities antitumor various other biological applications.

Language: Английский

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Smart stimuli-responsive polysaccharide nanohydrogels for drug delivery: a review

Journal of Materials Chemistry B, Journal Year: 2023, Volume and Issue: 11(44), P. 10538 - 10565

Published: Jan. 1, 2023

Polysaccharides have found extensive utilization as biomaterials in drug delivery systems owing to their remarkable biocompatibility, simple functionalization, and inherent biological properties.

Language: Английский

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