Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies

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

Опубликована: Март 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.

Язык: Английский

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The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions

Cancer Cell, Год журнала: 2024, Номер 42(4), С. 513 - 534

Опубликована: Апрель 1, 2024

Язык: Английский

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Cold and hot tumors: from molecular mechanisms to targeted therapy

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

Опубликована: Окт. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Язык: Английский

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Ferroptosis‐Enhanced Immunotherapy with an Injectable Dextran‐Chitosan Hydrogel for the Treatment of Malignant Ascites in Hepatocellular Carcinoma

Advanced Science, Год журнала: 2023, Номер 10(20)

Опубликована: Май 3, 2023

Abstract Malignant ascites in advanced hepatocellular carcinoma (HCC) is a complex clinical problem that lacks effective treatments. Due to the insensitivity of HCC cells traditional chemotherapies, low drug accumulation, and limited residence time peritoneal cavity, therapeutic effects malignant are not satisfactory. In this study, an injectable hydrogel delivery system based on chitosan hydrochloride oxidized dextran (CH‐OD) designed load sulfasalazine (SSZ), FDA‐approved with ferroptosis‐inducing ability, for tumor‐killing activation anti‐tumor immunity. Compared free SSZ, SSZ‐loaded CH‐OD (CH‐OD‐SSZ) exhibits greater cytotoxicity induces higher levels immunogenic ferroptosis. preclinical model hepatoma ascites, intraperitoneal administration CH‐OD‐SSZ can significantly suppress tumor progression improve immune landscape. Both vitro vivo, repolarization macrophages M1‐like phenotype promotes maturation dendritic cells. Combination treatment anti‐programmed cell death protein 1 (PD‐1) immunotherapy achieves more than 50% regression generates long‐term memory. Collectively, promising potential dissemination HCC, especially when combined anti‐PD‐1 immunotherapy.

Язык: Английский

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Chitosan- and hyaluronic acid-based nanoarchitectures in phototherapy: Combination cancer chemotherapy, immunotherapy and gene therapy

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 273, С. 132579 - 132579

Опубликована: Май 23, 2024

Язык: Английский

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Engineered Bio‐Based Hydrogels for Cancer Immunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(21)

Опубликована: Фев. 16, 2024

Immunotherapy represents a revolutionary paradigm in cancer management, showcasing its potential to impede tumor metastasis and recurrence. Nonetheless, challenges including limited therapeutic efficacy severe immune-related side effects are frequently encountered, especially solid tumors. Hydrogels, class of versatile materials featuring well-hydrated structures widely used biomedicine, offer promising platform for encapsulating releasing small molecule drugs, biomacromolecules, cells controlled manner. Immunomodulatory hydrogels present unique capability augmenting immune activation mitigating systemic toxicity through encapsulation multiple components localized administration. Notably, based on biopolymers have gained significant interest owing their biocompatibility, environmental friendliness, ease production. This review delves into the recent advances bio-based immunotherapy synergistic combinatorial approaches, highlighting diverse applications. It is anticipated that this will guide rational design field immunotherapy, fostering clinical translation ultimately benefiting patients.

Язык: Английский

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Harnessing Immunotherapy for Hepatocellular Carcinoma: Principles and Emerging Promises

Pathology - Research and Practice, Год журнала: 2025, Номер unknown, С. 155928 - 155928

Опубликована: Март 1, 2025

Язык: Английский

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The crosstalk between ferroptosis and anti‐tumor immunity in the tumor microenvironment: molecular mechanisms and therapeutic controversy

Cancer Communications, Год журнала: 2023, Номер 43(10), С. 1071 - 1096

Опубликована: Сен. 17, 2023

The advent of immunotherapy has significantly reshaped the landscape cancer treatment, greatly enhancing therapeutic outcomes for multiple types cancer. However, only a small subset individuals respond to it, underscoring urgent need new methods improve its response rate. Ferroptosis, recently discovered form programmed cell death, emerged as promising approach anti-tumor therapy, with targeting ferroptosis kill tumors seen potentially effective strategy. Numerous studies suggest that inducing can synergistically enhance effects immunotherapy, paving way combined treatment method in future. Nevertheless, recent research raised concerns about potential negative impacts on immunity consequence ferroptosis, leading conflicting views within scientific community interplay between and immunity, thereby necessity comprehensive review existing literature this relationship. Previous reviews have touched related content, many focusing primarily promoting role while overlooking evidence inhibitory immunity. Others concentrated solely discussing content either from perspective cells or immune ferroptosis. Given both exist tumor microenvironment, one-sided discussion cannot comprehensively summarize topic. Therefore, perspectives tumor-infiltrating cells, we systematically current intending provide explanations identify work needed establish translational basis ferroptosis-targeted therapy treating tumors.

Язык: Английский

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Monitoring ROS Responsive Fe₃O₄‐based Nanoparticle Mediated Ferroptosis and Immunotherapy via ¹²⁹Xe MRI

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(22)

Опубликована: Март 29, 2024

The immune checkpoint blockade strategy has improved the survival rate of late-stage lung cancer patients. However, low response limits immunotherapy efficiency. Here, we report a ROS-responsive Fe

Язык: Английский

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Mitochondria‐Targeted Multifunctional Nanoparticles Combine Cuproptosis and Programmed Cell Death‐1 Downregulation for Cancer Immunotherapy

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Июль 16, 2024

The combination of cuproptosis and immune checkpoint inhibition has shown promise in treating malignant tumors. However, it remains a challenge to deliver copper ions inhibitors efficiently simultaneously Herein, mitochondria-targeted nanoscale coordination polymer particle, Cu/TI, comprising Cu(II), triphenylphosphonium conjugate 5-carboxy-8-hydroxyquinoline (TI), for effective induction programmed cell death-1 (PD-L1) downregulation is reported. Upon systemic administration, Cu/TI accumulates tumor tissues induce immunogenic cancer death reduce PD-L1 expression. Consequently, promotes the intratumoral infiltration activation cytotoxic T lymphocytes greatly inhibit progression colorectal carcinoma triple-negative breast mouse models without causing obvious side effects.

Язык: Английский

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