Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Авг. 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.

Язык: Английский

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Cuproptosis in cancer: biological implications and therapeutic opportunities

Cellular & Molecular Biology Letters, Год журнала: 2024, Номер 29(1)

Опубликована: Июнь 25, 2024

Abstract Cuproptosis, a newly identified copper (Cu)-dependent form of cell death, stands out due to its distinct mechanism that sets it apart from other known death pathways. The molecular underpinnings cuproptosis involve the binding Cu lipoylated enzymes in tricarboxylic acid cycle. This interaction triggers enzyme aggregation and proteotoxic stress, culminating death. specific has yet be fully elucidated. recognized sparked numerous investigations into role tumorigenesis cancer therapy. In this review, we summarized current knowledge on metabolism link cancer. Furthermore, delineated mechanisms roles cuproptosis-related genes Finally, offered comprehensive discussion most recent advancements ionophores nanoparticle delivery systems utilize as cutting-edge strategy for treatment.

Язык: Английский

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Copper homeostasis and cuproptosis in health and disease

MedComm, Год журнала: 2024, Номер 5(10)

Опубликована: Сен. 17, 2024

Copper is a vital trace element in human physiology, essential for the synthesis of numerous crucial metabolic enzymes and facilitation various biological processes. Regulation copper levels within narrow range imperative maintaining homeostasis. Numerous studies have demonstrated significant roles homeostasis cuproptosis health disease pathogenesis. However, comprehensive up-to-date systematic review this domain remains absent. This aims to consolidate recent advancements understanding disease, focusing on underlying mechanisms potential therapeutic interventions. Dysregulation homeostasis, manifesting as either excess or deficiency, implicated etiology diseases. Cuproptosis, recently identified form cell death, characterized by intracellular overload. phenomenon mediates diverse array evolutionary processes organisms, spanning from genetic disorders, liver diseases, neurodegenerative cancers. provides summary pathogenic along with associated targeted agents. Furthermore, it explores future research directions yield treatment, management, prevention.

Язык: Английский

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Copper‐Induced Supramolecular Peptide Assemblies for Multi‐pathway Cell Death and Tumor Inhibition

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(34)

Опубликована: Июнь 5, 2024

Although self-assembly has emerged as an effective tool for fabricating biomaterials, achieving precise control over the morphologies and functionalities of resultant assemblies remains ongoing challenge. Inspired by copper peptide naturally present in human plasma, this study, we designed a synthetic precursor, FcGH. FcGH can self-assemble via two distinct pathways: spontaneous Cu

Язык: Английский

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Copper homeostasis and copper-induced cell death in tumor immunity: implications for therapeutic strategies in cancer immunotherapy

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Окт. 31, 2024

Copper is an important trace element for maintaining key biological functions such as cellular respiration, nerve conduction, and antioxidant defense. Maintaining copper homeostasis critical human health, its imbalance has been linked to various diseases, especially cancer. Cuproptosis, a novel mechanism of copper-induced cell death, provides new therapeutic opportunities metal ion regulation interact with fate. This review insights into the complex mechanisms metabolism, molecular basis cuproptosis, association cancer development. We assess role cuproptosis-related genes (CRGs) associated tumorigenesis, their importance prognostic indicators targets, impact on tumor microenvironment (TME) immune response. Ultimately, this highlights interplay between copper, immunotherapy.

Язык: Английский

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Synergistic enhancement of low-dose radiation therapy via cuproptosis and metabolic reprogramming for radiosensitization in in situ hepatocellular carcinoma

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Дек. 19, 2024

Radiotherapy (RT) is a primary clinical approach for cancer treatment, but its efficacy often hindered by various challenges, especially radiation resistance, which greatly compromises the therapeutic effectiveness of RT. Mitochondria, central to cellular energy metabolism and regulation cell death, play critical role in mechanisms radioresistance. In this context, cuproptosis, novel copper-induced mitochondria-respiratory-dependent death pathway, offers promising avenue radiosensitization. study, an innovative theranostic nanoplatform was designed induce cuproptosis synergy with low-dose therapy (LDRT, i.e., 0.5–2 Gy) treatment situ hepatocellular carcinoma (HCC). This aims reverse hypoxic tumor microenvironment, promoting shift from glycolysis oxidative phosphorylation (OXPHOS), thereby enhancing sensitivity cuproptosis. Concurrently, Fenton-like reaction ensures sustained supply copper depletion glutathione (GSH), inducing disrupting mitochondrial function, interrupting supply. strategy effectively overcomes radioresistance enhances against tumors. conclusion, study elucidates intricate interactions among hypoxia reversal, metabolic reprogramming, radiosensitization, particularly context treating carcinoma, providing paradigm radiotherapy.

Язык: Английский

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DDX10 Exacerbates Exosomal PD-L1 Dependent T Cell Exhaustion via Phase Separation of Rab27b in Oral Squamous Cell Carcinoma

Research, Год журнала: 2025, Номер 8

Опубликована: Янв. 1, 2025

DEAD-box ATPase 10 (DDX10), a prominent RNA-binding protein in the DDX family, has critical function cancer progression. Nevertheless, its well-defined mechanisms oral squamous cell carcinoma (OSCC) are still not well understood. Here, we identify that DDX10 is substantially increased OSCC, which positively correlated with poor prognosis and malignant behavior. Mechanistically, found had physical interaction Rab27b by undergoing phase separation. Knockdown of inhibited Rab27b-mediated exosome secretion expression programmed death-ligand 1 (PD-L1) within contents. Furthermore, knocking down could restore infiltration T cells, hence inhibiting progression OSCC. These findings highlight oncogenic role promoting exosomal PD-L1 via separation been preliminarily validated exhaustion A potential strategy for improving OSCC immunotherapy may involve inhibition DDX10.

Язык: Английский

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Engineered Cell Membrane Coating Technologies for Biomedical Applications: From Nanoscale to Macroscale

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Cell membrane coating has emerged as a promising strategy for the surface modification of biomaterials with biological membranes, serving cloak that can carry more functions. The cloaked inherit diverse intrinsic biofunctions derived from different cell sources, including enhanced biocompatibility, immunity evasion, specific targeting capacity, and immune regulation regenerative microenvironment. characteristics biomimicry biointerfacing have demonstrated versatility technology on variety biomaterials, thus, furthering research into wide range biomedical applications clinical translation. Here, preparation coatings is emphasized, sizes coated nanoscale to macroscale well engineering strategies introduce additional are summarized. Subsequently, utilization biomimetic membrane-cloaked in discussed, drug delivery, imaging phototherapy, cancer immunotherapy, anti-infection detoxification, implant modification. In conclusion, latest advancements preclinical studies, along multiple benefits membrane-coated nanoparticles (NPs) systems, elucidated.

Язык: Английский

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Hyperbaric Oxygen Regulates Tumor pH to Boost Copper‐Doped Hydroxyethyl Starch Conjugate Nanoparticles Against Cancer Stem Cells

Exploration, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

ABSTRACT An extracellular acidic environment and an intracellular mildly alkaline induced by carbonic anhydrase 9 (CA9) play a critical role in self‐renewal, invasion, migration, drug resistance of cancer stem cells (CSCs) within hypoxic solid tumors. Here, we report antitumor strategy leveraging hyperbaric oxygen therapy (HBO) to regulate tumor pH boost hydroxyethyl starch‐doxorubicin‐copper nanoparticles (HHD‐Cu NPs) against CSCs. HBO overcomes hypoxia, downregulates pH‐regulatory proteins such as CA9, leads accumulation metabolites. As result, promotes acidification both CSCs, triggering efficient doxorubicin release the potent copper‐mediated chemical dynamic effect subsequently administered dual‐acid‐responsive HHD‐Cu NPs. The combination with NPs not only eliminates but also inhibits altogether leading inhibition. This study explores new function clinical‐widely used establishes novel for treating CSCs abundant

Язык: Английский

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Copper‐Induced Supramolecular Peptide Assemblies for Multi‐pathway Cell Death and Tumor Inhibition

Angewandte Chemie, Год журнала: 2024, Номер 136(34)

Опубликована: Июнь 5, 2024

Abstract Although self‐assembly has emerged as an effective tool for fabricating biomaterials, achieving precise control over the morphologies and functionalities of resultant assemblies remains ongoing challenge. Inspired by copper peptide naturally present in human plasma, this study, we designed a synthetic precursor, FcGH. FcGH can self‐assemble via two distinct pathways: spontaneous Cu 2+ ‐induced. These assembly pathways enabled formation with tunable adjusting amount added . We found that nanoparticles formed ‐induced exhibited significantly higher cellular uptake efficiency than wormlike fibers spontaneously. Moreover, process occurred spontaneously at 1 : molar ratio to FcGH, avoiding excessive use tedious preparation procedure. By co‐assembling 10‐hydroxycamptothecin (HCPT)‐conjugated supramolecular nanodrugs elicited multiple cell death modalities cancer cells elevated immunogenicity, enhancing therapeutic effect compared free HCPT. This study highlights efficient directing synergistic tumor therapy.

Язык: Английский

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