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

---

Iron and copper: critical executioners of ferroptosis, cuproptosis and other forms of cell death

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 16, 2023

Abstract Regulated cell death (RCD) is a regulable that involves well-organized signaling cascades and molecular mechanisms. RCD implicated in fundamental processes such as organ production tissue remodeling, removing superfluous structures or cells, regulating numbers. Previous studies have not been able to reveal the complete mechanisms, novel methods of are constantly being proposed. Two metal ions, iron (Fe) copper (Cu) essential factors leading RCDs only induce ferroptosis cuproptosis, respectively but also lead impairment eventually diverse death. This review summarizes direct indirect mechanisms by which Fe Cu impede growth various forms mediated these two metals. Moreover, we aimed delineate interrelationships between with distinct pathways shedding light on complex intricate govern cellular survival Finally, prospects outlined this suggest approach for investigating death, may involve integrating current therapeutic strategies offer promising solution overcome drug resistance certain diseases.

Language: Английский

---

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

---

Ferroptosis: principles and significance in health and disease

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

Published: June 6, 2024

Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.

Language: Английский

---

Nanoparticles Synergize Ferroptosis and Cuproptosis to Potentiate Cancer Immunotherapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: March 13, 2024

Abstract The recent discovery of copper‐mediated and mitochondrion‐dependent cuproptosis has aroused strong interest in harnessing this novel mechanism cell death for cancer therapy. Here the design a core‐shell nanoparticle, CuP/Er, co‐delivery copper (Cu) erastin (Er) to cells synergistic ferroptosis is reported. anti‐Warburg effect Er sensitizes tumor Cu‐mediated cuproptosis, leading irreparable mitochondrial damage by depleting glutathione enhancing lipid peroxidation. CuP/Er induces immunogenic death, enhances antigen presentation, upregulates programmed death‐ligand 1 expression. Consequently, promotes proliferation infiltration T cells, when combined with immune checkpoint blockade, effectively reinvigorates mediate regression murine colon adenocarcinoma triple‐negative breast prevent metastasis. This study suggests unique opportunity synergize combination therapy nanoparticles elicit antitumor effects potentiate current immunotherapies.

Language: Английский

---

Copper homeostasis and cuproptosis in mitochondria

Life Sciences, Journal Year: 2023, Volume and Issue: 334, P. 122223 - 122223

Published: Oct. 29, 2023

Language: Английский

---

Crosstalk between ferroptosis and cuproptosis: From mechanism to potential clinical application

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116115 - 116115

Published: Jan. 5, 2024

Ferroptosis and cuproptosis, regulated forms of cell death resulting from metal ion accumulation, are closely related in terms occurrence, metabolism, signaling pathways, drug resistance. Notably, it is now understood that these processes play crucial roles regulating physiological pathological processes, especially tumor development. Consequently, ferroptosis cuproptosis have gained increasing significance as potential targets for anti-cancer This article systematically outlines the molecular mechanisms cross-talk components both elucidating their impacts on cancer. Furthermore, investigates clinical perspective targeted cancer chemotherapy, immunotherapy, radiotherapy. Our discussion extends to a comparative analysis nanoparticles developed based cancer, contrasting them with current conventional therapies. Opportunities challenges treatment explored, emphasizing therapeutic direction co-targeting cuproptosis. The also attempts analyze applications this approach while summarizing existing barriers require overcoming.

Language: Английский

---

Epigenetic regulation of diverse cell death modalities in cancer: a focus on pyroptosis, ferroptosis, cuproptosis, and disulfidptosis

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

Published: April 23, 2024

Abstract Tumor is a local tissue hyperplasia resulted from cancerous transformation of normal cells under the action various physical, chemical and biological factors. The exploration tumorigenesis mechanism crucial for early prevention treatment tumors. Epigenetic modification common important in cells, including DNA methylation, histone modification, non-coding RNA m6A modification. mode cell death programmed by death-related genes; however, recent researches have revealed some new modes death, pyroptosis, ferroptosis, cuproptosis disulfidptosis. regulation deaths mainly involved key proteins affects up-regulating or down-regulating expression levels proteins. This study aims to investigate epigenetic modifications regulating disulfidptosis tumor explore possible triggering factors development microscopic point view, provide potential targets therapy perspective antitumor drugs combination therapies.

Language: Английский

---

The crosstalk between copper-induced oxidative stress and cuproptosis: a novel potential anticancer paradigm

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

Published: July 5, 2024

Abstract Copper is a crucial trace element that plays role in various pathophysiological processes the human body. also acts as transition metal involved redox reactions, contributing to generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated different types regulated cell death. The recent discovery cuproptosis, copper-dependent death pathway distinct from other known forms, raised interest researchers field cancer therapy. Herein, present work aims outline current understanding with an emphasis on its anticancer activities through interplay copper-induced stress, thereby providing new ideas for therapeutic approaches targeting modes future.

Language: Английский

---

Cellular Trojan Horse initiates bimetallic Fe-Cu MOF-mediated synergistic cuproptosis and ferroptosis against malignancies

Science Advances, Journal Year: 2024, Volume and Issue: 10(15)

Published: April 10, 2024

Disruptions in metal balance can trigger a synergistic interplay of cuproptosis and ferroptosis, offering promising solutions to enduring challenges oncology. Here, we have engineered Cellular Trojan Horse, named MetaCell, which uses live neutrophils stably internalize thermosensitive liposomal bimetallic Fe-Cu MOFs (Lip@Fe-Cu-MOFs). MetaCell instigate thereby enhancing treatment efficacy. Mirroring the characteristics neutrophils, evade immune system not only infiltrate tumors but also respond inflammation by releasing therapeutic components, surmounting traditional barriers. Notably, Lip@Fe-Cu-MOFs demonstrate notable photothermal effects, inciting targeted release Fe-Cu-MOFs within cancer cells amplifying action ferroptosis. has demonstrated outcomes tumor-bearing mice, effectively eliminating solid forestalling recurrence, leading extended survival. This research provides great insights into complex between copper iron homeostasis malignancies, potentially paving way for innovative approaches treatment.

Language: Английский

---