Cuproptosis: mechanisms and links with cancers

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Март 7, 2023

Abstract Cuproptosis was a copper-dependent and unique kind of cell death that separate from existing other forms death. The last decade has witnessed considerable increase in investigations programmed death, whether copper induced an independent form long been argued until mechanism cuproptosis revealed. After that, increasing number researchers attempted to identify the relationship between process cancer. Thus, this review, we systematically detailed systemic cellular metabolic processes copper-related tumor signaling pathways. Moreover, not only focus on discovery its mechanism, but also outline association cancers. Finally, further highlight possible therapeutic direction employing ion ionophores with cuproptosis-inducing functions combination small molecule drugs for targeted therapy treat specific

Язык: Английский

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Elesclomol: a copper ionophore targeting mitochondrial metabolism for cancer therapy

Journal of Experimental & Clinical Cancer Research, Год журнала: 2022, Номер 41(1)

Опубликована: Сен. 12, 2022

Abstract Elesclomol is an anticancer drug that targets mitochondrial metabolism. In the past, elesclomol was recognized as inducer of oxidative stress, but now it has also been found to suppress cancer by inducing cuproptosis. Elesclomol’s activity determined dependence on The metabolism stem cells, cells resistant platinum drugs, proteasome inhibitors, molecularly targeted and with inhibited glycolysis significantly enhanced. exhibited tremendous toxicity all three kinds cells. Elesclomol's highly dependent its transport extracellular copper ions, a process involved in discovery cuproptosis perfected specific suppressor mechanism elesclomol. For some time, failed yield favorable results oncology clinical trials, safety application confirmed. Research progress relationship between elesclomol, provides possibility explore reapplication clinic. New trials should selectively target types high attempt combine platinum, or inhibitors. Herein, particular will be presented, which may shed light better tumor treatment.

Язык: Английский

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An Overview: The Diversified Role of Mitochondria in Cancer Metabolism

International Journal of Biological Sciences, Год журнала: 2023, Номер 19(3), С. 897 - 915

Опубликована: Янв. 1, 2023

Mitochondria are intracellular organelles involved in energy production, cell metabolism and signaling.They essential not only the process of ATP synthesis, lipid nucleic acid metabolism, but also tumor development metastasis.Mutations mtDNA commonly found cancer cells to promote rewiring bioenergetics biosynthesis, various metabolites especially oncometabolites mitochondria regulate progression.And mutation enzymes TCA cycle leads unusual accumulation certain oncometabolites.Mitochondria have been demonstrated as target for treatment.Cancer rely on two main resources: oxidative phosphorylation (OXPHOS) glycolysis.By manipulating OXPHOS genes or adjusting production mitochondria, growth can be restrained.For example, enhanced complex I activity increases NAD + /NADH prevent metastasis progression cancers.In this review, we discussed mitochondrial function specially explored unique role stem microenvironment.Targeting pathway mitochondria-related emerging a potential therapeutic strategy cancers.

Язык: Английский

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Metabolic reprogramming in cholangiocarcinoma

Journal of Hepatology, Год журнала: 2022, Номер 77(3), С. 849 - 864

Опубликована: Май 18, 2022

Язык: Английский

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PANoptosis: Mechanisms, biology, and role in disease

Immunological Reviews, Год журнала: 2023, Номер 321(1), С. 246 - 262

Опубликована: Окт. 12, 2023

Summary Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which mediated by multifaceted PANoptosome complexes assembled via integrating components from other modalities. There growing interest in process function of PANoptosis. Accumulating evidence suggests that occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, cancer. Given impact across disease spectrum, this review briefly describes relationships highlights key molecules formation activation, outlines roles diseases together with potential therapeutic targeting. We also discuss important concepts pressing issues future research. Improved understanding its mechanisms crucial identifying novel targets strategies.

Язык: Английский

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Metabolic reprogramming and its clinical implication for liver cancer

Hepatology, Год журнала: 2023, Номер 78(5), С. 1602 - 1624

Опубликована: Янв. 3, 2023

Cancer cells often encounter hypoxic and hypo-nutrient conditions, which force them to make adaptive changes meet their high demands for energy various biomaterials biomass synthesis. As a result, enhanced catabolism (breakdown of macromolecules production) anabolism (macromolecule synthesis from bio-precursors) are induced in cancer. This phenomenon is called “metabolic reprogramming,” cancer hallmark contributing development, metastasis, drug resistance. HCC cholangiocarcinoma (CCA) 2 different liver cancers with intertumoral heterogeneity terms etiologies, mutational landscapes, transcriptomes, histological representations. In agreement, metabolism or CCA remarkably heterogeneous, although the glycolytic pathways an increase generation lactate (the Warburg effect) have been frequently detected those tumors. For example, tumors activated β-catenin addicted fatty acid catabolism, whereas derived avoid using acids. this review, we describe common metabolic alterations as well features unique subsets. We discuss NAFLD well, because will likely become leading etiology coming years due obesity epidemic Western world. Furthermore, outline clinical implication highlight computation systems biology approaches, such genome-wide models, valuable tool allowing us identify therapeutic targets develop personalized treatments patients.

Язык: Английский

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Hallmarks of cancer stemness

Cell stem cell, Год журнала: 2024, Номер 31(5), С. 617 - 639

Опубликована: Май 1, 2024

Язык: Английский

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Mitochondrial quality control in human health and disease

Military Medical Research, Год журнала: 2024, Номер 11(1)

Опубликована: Май 29, 2024

Abstract Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable vital life processes such cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key like biogenesis, dynamics, mitophagy, which have garnered increasing attention from researchers unveil specific molecular mechanisms. this review, we present comprehensive summary of primary mechanisms functions regulators involved major components MQC. Furthermore, critical regulated by MQC its diverse roles progression systemic diseases been described detail. We discuss agonists antagonists targeting MQC, aiming explore potential therapeutic research prospects enhancing stabilize function.

Язык: Английский

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Copper metabolism and cuproptosis in human malignancies: Unraveling the complex interplay for therapeutic insights

Heliyon, Год журнала: 2024, Номер 10(5), С. e27496 - e27496

Опубликована: Март 1, 2024

Copper, a vital trace element, orchestrates diverse cellular processes ranging from energy production to antioxidant defense and angiogenesis. Copper metabolism cuproptosis are closely linked in the context of human diseases, with particular focus on cancer. Cuproptosis refers specific type copper-mediated cell death or copper toxicity triggered by disruptions within cells. This phenomenon encompasses spectrum mechanisms, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum perturbations metal ion equilibrium. Mechanistically, is driven binding lipoylated enzymes tricarboxylic acid (TCA) cycle. interaction participates protein aggregation proteotoxic ultimately culminating death. Targeting its associated pathways cancer cells holds therapeutic potential selectively targeting eliminating cancerous Strategies modulate levels, enhance excretion, interfere cuproptotic being explored identify novel targets for therapy improve patient outcomes. Understanding relationship between malignancies remains an active area research. review provides comprehensive overview association metabolism, homeostasis, cancers, explicitly emphasizing mechanism implications pathogenesis. Additionally, we emphasize aspects treatment.

Язык: Английский

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Multi-stage mechanisms of tumor metastasis and therapeutic strategies

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 11, 2024

The cascade of metastasis in tumor cells, exhibiting organ-specific tendencies, may occur at numerous phases the disease and progress under intense evolutionary pressures. Organ-specific relies on formation pre-metastatic niche (PMN), with diverse cell types complex interactions contributing to this concept, adding a new dimension traditional cascade. Prior metastatic dissemination, as orchestrators PMN formation, primary tumor-derived extracellular vesicles prepare fertile microenvironment for settlement colonization circulating cells distant secondary sites, significantly impacting cancer progression outcomes. Obviously, solely intervening sites passively after macrometastasis is often insufficient. Early prediction holistic, macro-level control represent future directions therapy. This review emphasizes dynamic intricate systematic alterations that progresses, illustrates immunological landscape creation, deepens understanding treatment modalities pertinent metastasis, thereby identifying some prognostic predictive biomarkers favorable early predict occurrence design appropriate combinations.

Язык: Английский

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