Ferroptosis in cancer and cancer immunotherapy

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(2), P. 88 - 116

Published: Feb. 1, 2022

Abstract The hallmark of tumorigenesis is the successful circumvention cell death regulation for achieving unlimited replication and immortality. Ferroptosis a newly identified type dependent on lipid peroxidation which differs from classical programmed in terms morphology, physiology biochemistry. broad spectrum injury tumor tolerance are main reasons radiotherapy chemotherapy failure. effective rate immunotherapy as new treatment method less than 30%. can be seen radiotherapy, chemotherapy, immunotherapy; therefore, ferroptosis activation may potential strategy to overcome drug resistance mechanism traditional cancer treatments. In this review, characteristics causes by briefly described. addition, three metabolic regulations its crosstalk with signaling pathways summarized. Collectively, these findings suggest vital role based interaction immunotherapy, thus, indicating remarkable treatment.

Language: Английский

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Recent advances in nanomedicines for photodynamic therapy (PDT)-driven cancer immunotherapy

Theranostics, Journal Year: 2021, Volume and Issue: 12(1), P. 434 - 458

Published: Dec. 15, 2021

Cancer immunotherapy has made tremendous clinical progress in advanced-stage malignancies. However, patients with various tumors exhibit a low response rate to because of powerful immunosuppressive tumor microenvironment (TME) and insufficient immunogenicity tumors. Photodynamic therapy (PDT) can not only directly kill cells, but also elicit immunogenic cell death (ICD), providing antitumor immunity. Unfortunately, limitations from the inherent nature complex TME significantly reduce efficiency PDT. Recently, smart nanomedicine-based strategies could subtly modulate pharmacokinetics therapeutic compounds optimize both PDT immunotherapy, resulting an improved effect. Here, emerging nanomedicines for PDT-driven cancer are reviewed, including hypoxia-reversed nanomedicines, nanosized metal-organic frameworks, subcellular targeted nanoparticles (NPs). Moreover, we highlight synergistic nanotherapeutics used amplify immune responses combined against Lastly, challenges future expectations field discussed.

Language: Английский

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Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy

Cell Metabolism, Journal Year: 2022, Volume and Issue: 35(1), P. 84 - 100.e8

Published: Oct. 17, 2022

Treatment of triple-negative breast cancer (TNBC) remains challenging. Deciphering the orchestration metabolic pathways in regulating ferroptosis will provide new insights into TNBC therapeutic strategies. Here, we integrated multiomics data our large cohort (n = 465) to develop atlas. We discovered that TNBCs had heterogeneous phenotypes ferroptosis-related metabolites and pathways. The luminal androgen receptor (LAR) subtype was characterized by upregulation oxidized phosphatidylethanolamines glutathione metabolism (especially GPX4), which allowed utilization GPX4 inhibitors induce ferroptosis. Furthermore, verified inhibition not only induced tumor but also enhanced antitumor immunity. combination anti-PD1 possessed greater efficacy than monotherapy. Clinically, higher expression correlated with lower cytolytic scores worse prognosis immunotherapy cohorts. Collectively, this study demonstrated landscape revealed an innovative strategy for refractory LAR tumors.

Language: Английский

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System Xc−/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 29, 2022

The activation of ferroptosis is a new effective way to treat drug-resistant solid tumors. Ferroptosis an iron-mediated form cell death caused by the accumulation lipid peroxides. intracellular imbalance between oxidant and antioxidant due abnormal expression multiple redox active enzymes will promote produce reactive oxygen species (ROS). So far, few pathways regulators have been discovered regulate ferroptosis. In particular, cystine/glutamate antiporter (System X c − ), glutathione peroxidase 4 (GPX4) (GSH) /GSH/GPX4 axis) plays key role in preventing peroxidation-mediated ferroptosis, because which could be inhibited blocking System axis. This review aims present current understanding mechanism based on axis treatment

Language: Английский

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Recent progress in ferroptosis: inducers and inhibitors

Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: Dec. 29, 2022

Ferroptosis is a new iron-dependent form of programmed cell death characterized by iron accumulation and lipid peroxidation. In recent years, ferroptosis has garnered enormous interest in disease treatment research communities pursuit to reveal the mechanism key targets because closely related pathophysiological processes many diseases. Recent studies have shown some targets, such as glutathione peroxidase 4 (GPX4) System Xc-, several inducers inhibitors been developed regulate these targets. With emergence on made developments. The selection use are very important for work. This paper briefly introduces regulatory metabolic pathway, lists categorizes commonly used recently inhibitors, discusses their medical application. ends with potential future direction ferroptosis.

Language: Английский

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A Hollow Amorphous Bimetal Organic Framework for Synergistic Cuproptosis/Ferroptosis/Apoptosis Anticancer Therapy via Disrupting Intracellular Redox Homeostasis and Copper/Iron Metabolisms

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(40)

Published: July 30, 2022

Abstract Cuproptosis is a very newly recognized regulated cell death modality that distinct from known mechanisms and shows enormous prospect in cancer treatment. However, its efficacy copper‐dependent restricted by strictly copper metabolism. Herein, novel copper/iron hybrid hollow amorphous metal organic framework (HaMOF) developed as an oxidative stress amplifier metabolic disrupter for synergistic cuproptosis/ferroptosis/apoptosis anticancer therapy. The HaMOF fabricated Cu 2+ , 3,3′‐dithiobis(propionohydrazide) Fe 3+ via unsaturated coordination‐etching integration strategy, then doxorubicin loaded followed surface decoration with hyaluronan. obtained DOX@Fe/CuTH exhibits tumor microenvironment‐triggered catalytic therapeutic property, wherein it can amplify cellular simultaneously boosting H 2 O production depleting glutathione. Moreover, cause mitochondrial dysfunction downregulate the expressions of transporter ATP7A iron FPN 1, thereby leading to disorders high retentions cytoplasm •OH generation. overloaded lipoylated protein dihydrolipoamide S‐acetyltransferase aggregation lead cuproptosis. Collectively, both augmented induce potent ferroptosis, which synergizes cuproptosis DOX‐mediated apoptosis efficiently suppress growth. This bimetallic nanoplatform provides new paradigm boost cuproptosis‐related therapies.

Language: Английский

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Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Language: Английский

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Engineering Multienzyme‐Mimicking Covalent Organic Frameworks as Pyroptosis Inducers for Boosting Antitumor Immunity

Advanced Materials, Journal Year: 2021, Volume and Issue: 34(13)

Published: Dec. 17, 2021

The engineering of a series multienzyme-mimicking covalent organic frameworks (COFs), COF-909-Cu, COF-909-Fe, and COF-909-Ni, as pyroptosis inducers, remodeling the tumor microenvironment to boost cancer immunotherapy, is reported. Mechanistic studies reveal that these COFs can serve hydrogen peroxide (H

Language: Английский

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A “Closed‐Loop” Therapeutic Strategy Based on Mutually Reinforced Ferroptosis and Immunotherapy

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(13)

Published: Feb. 1, 2022

Abstract The immunosuppression and immune escape of current immunotherapy result in low efficacy, ferroptosis is greatly restricted by the reactive oxygen species (ROS) production efficiency. Here, for first time a “closed‐loop” therapy based on photothermal enhancement stimulated each other multifunctional nanoplatform reported. This platform composed copper silicate iron mesoporous hollow nanospheres, followed situ growth Au nanoparticles loading an adjuvant resiquimod R848. laser irradiation‐mediated heat introduction ions significantly enhance ROS generation, leading to simultaneous depletion glutathione peroxidase 4 (GPX4) (GSH). onset tumor cells thus enhanced response with immunogenic cell death (ICD) triggered, promoting dendritic (DCs) maturation T infiltration. Interferon γ (IFN‐γ) released from CD8 + downregulates expression SLC7A11 GPX4, which turn enhances expression, constituting “closed‐Loop” therapy. Importantly, this system effective both killing primary inhibiting metastasis. proposed therapeutic strategy may provide guidance design future antitumor nanoplatforms.

Language: Английский

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Engineered bioorthogonal POLY-PROTAC nanoparticles for tumour-specific protein degradation and precise cancer therapy

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 26, 2022

Abstract PROteolysis TArgeting Chimeras (PROTACs) has been exploited to degrade putative protein targets. However, the antitumor performance of PROTACs is impaired by their insufficient tumour distribution. Herein, we present de novo designed polymeric PROTAC (POLY-PROTAC) nanotherapeutics for tumour-specific degradation. The POLY-PROTACs are engineered covalently grafting small molecular onto backbone an amphiphilic diblock copolymer via disulfide bonds. self-assemble into micellar nanoparticles and sequentially respond extracellular matrix metalloproteinase-2, intracellular acidic reductive microenvironment. POLY-PROTAC NPs further functionalized with azide groups bioorthogonal click reaction-amplified delivery tissue. For proof-of-concept, demonstrate that BRD4 degradation nanoplatform combine photodynamic therapy efficiently regress xenografts in a mouse model MDA-MB-231 breast cancer. This study suggests potential precise PROTAC-based cancer therapy.

Language: Английский

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