Emerging role of immunogenic cell death in cancer immunotherapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 10, 2024

Cancer immunotherapy, such as immune checkpoint blockade (ICB), has emerged a groundbreaking approach for effective cancer treatment. Despite its considerable potential, clinical studies have indicated that the current response rate to immunotherapy is suboptimal, primarily attributed low immunogenicity in certain types of malignant tumors. Immunogenic cell death (ICD) represents form regulated (RCD) capable enhancing tumor and activating tumor-specific innate adaptive responses immunocompetent hosts. Therefore, gaining deeper understanding ICD evolution crucial developing more therapeutic strategies. This review focuses exclusively on both historical recent discoveries related modes their mechanistic insights, particularly within context immunotherapy. Our findings are also highlighted, revealing mode induction facilitated by atypical interferon (IFN)-stimulated genes (ISGs), including polo-like kinase 2 ( PLK2 ), during hyperactive type I IFN signaling. The concludes discussing potential ICD, with special attention relevance preclinical settings field

Language: Английский

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Epigenetic modification of ferroptosis by non-coding RNAs in cancer drug resistance

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 27, 2024

Abstract The development of drug resistance remains a major challenge in cancer treatment. Ferroptosis, unique type regulated cell death, plays pivotal role inhibiting tumour growth, presenting new opportunities treating chemotherapeutic resistance. Accumulating studies indicate that epigenetic modifications by non-coding RNAs (ncRNA) can determine vulnerability to ferroptosis. In this review, we first summarize the growth/development. Then, core molecular mechanisms ferroptosis, its upstream regulation, and downstream effects on Finally, review recent advances understanding how ncRNAs regulate ferroptosis from such modulate This aims enhance general ncRNA-mediated regulatory which highlighting ncRNA-ferroptosis axis as key druggable target overcoming

Language: Английский

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EZH2 suppresses ferroptosis in hepatocellular carcinoma and reduces sorafenib sensitivity through epigenetic regulation of TFR2

Cancer Science, Journal Year: 2024, Volume and Issue: 115(7), P. 2220 - 2234

Published: April 16, 2024

Enhancing sensitivity to sorafenib can significantly extend the duration of resistance it, offering substantial benefits for treating patients with hepatocellular carcinoma (HCC). However, role ferroptosis in influencing within HCC remains pivotal. The enhancer zeste homolog 2 (EZH2) plays a significant promoting malignant progression HCC, yet relationship between ferroptosis, sensitivity, and EZH2 is not entirely clear. Bioinformatic analysis indicates elevated expression predicting an unfavorable prognosis. Overexpressing drive cell proliferation while simultaneously reducing ferroptosis. Further reveals that amplifies modification H3K27 me3, thereby TFR2 expression. This results decreased RNA polymerase II binding promoter region, leading reduced Knocking down cells. In sorafenib-resistant HepG2(HepG2-SR) cells, increased. Moreover, combining tazemetostat-an inhibitor-with demonstrates synergistic ferroptosis-promoting effects HepG2-SR conclusion, our study illustrates how epigenetically regulates through suppressing combination tazemetostat exhibits superior anticancer therapy sensitizes cells sorafenib, shedding new light on delaying ameliorating resistance.

Language: Английский

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Ferroptosis and EMT resistance in cancer: a comprehensive review of the interplay

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 26, 2024

Ferroptosis differs from traditional cell death mechanisms like apoptosis, necrosis, and autophagy, primarily due to its reliance on iron metabolism the loss of glutathione peroxidase activity, leading lipid peroxidation death. The dysregulation is a hallmark various cancers, contributing tumor progression, metastasis, notably, drug resistance. acquisition mesenchymal characteristics by epithelial cells known as Epithelial–Mesenchymal Transition (EMT), biological process intricately linked cancer development, promoting traits such invasiveness, resistance therapeutic interventions. EMT plays pivotal role in progression contributes significantly complex dynamics carcinogenesis. Research findings indicate that exhibit greater susceptibility ferroptosis compared their counterparts. induction becomes more effective eliminating drug-resistant during EMT. interplay between EMT, where transform into mobile cells, crucial understanding progression. associated with increased metastasis review delves how influence each other, highlighting key proteins GPX4, which protects against peroxidation, inhibition can induce ferroptosis. Conversely, GPX4 expression heightened cells. Moreover, discusses implications EMT-induced transcription factors Snail, Zeb1, Twist modulating sensitivity ferroptosis, thereby affecting treatment outcomes. Targeting pathway offers promising strategy, particularly for tumors resistant conventional treatments. these could potentially overcome However, translating clinical practice presents challenges, including precise induction, identifying predictive biomarkers, optimizing combination therapies. underscores need further research unravel interactions cancer. This lead development effective, targeted treatments, tumors, offering new hope therapeutics.

Language: Английский

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Ferroptosis targeting natural compounds as a promising approach for developing potent liver cancer agents

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 26, 2024

Liver cancer is the second leading cause of cancer-related death worldwide. However, treatment options, including surgical resection, transplantation, and molecular drug therapies, are limited effectiveness. Recent studies have demonstrated that suppressing ferroptosis might be a pivotal signal for liver initiation, thus providing new way to combat cancer. Ferroptosis distinct form controlled cell differs from conventional routes like apoptosis, necrosis, pyroptosis. It results intracellular iron overload, which raises iron-dependent reactive oxygen species. This, in turn, leads accumulation lipid peroxides further result oxidative damage membranes, disrupt normal functioning, ultimately speed up phenomenon. regulation intricately linked cellular physiological processes, encompassing metabolism, equilibrium between oxygen-free radical reactions peroxidation. This review intends summarize natural compounds targeting offer therapeutic ideas Furthermore, it serves as foundation identifying applying chemical medicines chemicals target treat efficiently.

Language: Английский

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Ferroptosis in Cancer Therapy: Mechanisms, Small Molecule Inducers, and Novel Approaches

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 2485 - 2529

Published: June 1, 2024

Abstract: Ferroptosis, a unique form of programmed cell death, is initiated by an excess iron accumulation and lipid peroxidation-induced damage. There growing body evidence indicating that ferroptosis plays critical role in the advancement tumors. The increased metabolic activity higher levels tumor cells make them particularly vulnerable to ferroptosis. As result, targeted induction becoming increasingly promising approach for cancer treatment. This review offers overview regulatory mechanisms ferroptosis, delves into mechanism action traditional small molecule inducers their effects on various In addition, latest progress inducing using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic (SDT) nanomaterials summarized. Finally, this discusses challenges opportunities development ferroptosis-inducing agents, focusing discovering targets, improving selectivity, reducing toxic side effects. Keywords: inducers, molecules, PROTACs, PDT, SDT,

Language: Английский

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Machine learning and molecular subtyping reveal the impact of diverse patterns of cell death on the prognosis and treatment of hepatocellular carcinoma

Computational Biology and Chemistry, Journal Year: 2025, Volume and Issue: 115, P. 108360 - 108360

Published: Jan. 27, 2025

Language: Английский

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Recent advancements in nanomaterial-mediated ferroptosis-induced cancer therapy: Importance of molecular dynamics and novel strategies

Life Sciences, Journal Year: 2024, Volume and Issue: 346, P. 122629 - 122629

Published: April 15, 2024

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs other forms death, such as apoptosis necrosis. Molecular therapeutics have hard time playing the long-acting role ferroptosis induction due to their limited water solubility, low targeting capacity, quick metabolism vivo. To this end, small molecule inducers based on biological factors long been used strategy induce death. Research into advancements nanotechnology led discovery that nanomaterials are superior medications triggering ferroptosis. Nanomaterials derived iron can enhance by directly releasing large quantities increasing ROS levels. Moreover, utilizing promote programmed minimizes probability unfavorable effects induced mutations cancer-associated genes RAS TP53. Taken together, review summarizes molecular mechanisms involved along with classification induction. also emphasized importance organelles control cancer therapy. The trigger categorized explained. Iron-based noniron-based characterization at cellular levels explored, which will be useful for inducing leads reduced tumor growth. Within framework, we offer synopsis, traverses well-established mechanism offers practical suggestions design therapeutic use nanomaterials.

Language: Английский

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DAB2⁺ macrophages support FAP⁺ fibroblasts in shaping tumor barrier and inducing poor clinical outcomes in liver cancer

Theranostics, Journal Year: 2024, Volume and Issue: 14(12), P. 4822 - 4843

Published: Jan. 1, 2024

Cancer-associated fibroblasts (CAFs) are the key components of immune barrier in liver cancer. Therefore, gaining a deeper understanding heterogeneity and intercellular communication CAFs holds utmost importance boosting immunotherapy effectiveness improving clinical outcomes.

Language: Английский

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Targeting Metabolic–Redox Nexus to Regulate Drug Resistance: From Mechanism to Tumor Therapy

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 828 - 828

Published: July 10, 2024

Drug resistance is currently one of the biggest challenges in cancer treatment. With deepening understanding drug resistance, various mechanisms have been revealed, including metabolic reprogramming and alterations redox balance. Notably, mediates survival tumor cells harsh environments, thereby promoting development resistance. In addition, changes during pattern shift trigger reactive oxygen species (ROS) production, which turn regulates cellular metabolism, DNA repair, cell death, metabolism direct or indirect ways to influence sensitivity tumors therapies. Therefore, intersection ROS profoundly affects clarifying entangled may be beneficial for developing drugs treatment methods thwart this review, we will summarize regulatory mechanism on highlight recent therapeutic strategies targeting metabolic-redox circuits, dietary interventions, novel chemosynthetic drugs, combination regimens, delivery systems.

Language: Английский

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