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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The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

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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

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Ferroptosis, necroptosis, and pyroptosis in cancer: Crucial cell death types in radiotherapy and post-radiotherapy immune activation

Radiotherapy and Oncology, Journal Year: 2023, Volume and Issue: 184, P. 109689 - 109689

Published: May 6, 2023

Language: Английский

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The Cancer Antioxidant Regulation System in Therapeutic Resistance

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 778 - 778

Published: June 27, 2024

Antioxidants play a pivotal role in neutralizing reactive oxygen species (ROS), which are known to induce oxidative stress. In the context of cancer development, cells adeptly maintain elevated levels both ROS and antioxidants through process termed "redox reprogramming". This balance optimizes proliferative influence while simultaneously reducing potential for cause damage cell. some cases, adapted antioxidant machinery can hamper efficacy treatments neoplastic diseases, representing significant facet resistance mechanisms observed therapy. this review, we outline contribution systems therapeutic resistance. We detail fundamental constituents these systems, encompassing central regulatory involving transcription factors (of particular importance is KEAP1/NRF2 signaling axis), molecular effectors antioxidants, auxiliary responsible NADPH generation. Furthermore, present recent clinical trials based on targeted treatment cancer, assessing as well challenges strategy Additionally, summarize pressing issues field, with aim illuminating path toward emergence novel anticancer approaches by orchestrating redox signaling.

Language: Английский

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CRISPR/Cas9 screen reveals that targeting TRIM34 enhances ferroptosis sensitivity and augments immunotherapy efficacy in hepatocellular carcinoma

Cancer Letters, Journal Year: 2024, Volume and Issue: 593, P. 216935 - 216935

Published: May 3, 2024

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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WT161, a selective HDAC6 inhibitor, decreases growth, enhances chemosensitivity, promotes apoptosis, and suppresses motility of melanoma cells

Cancer Chemotherapy and Pharmacology, Journal Year: 2025, Volume and Issue: 95(1)

Published: Jan. 17, 2025

Language: Английский

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Targeting ferroptosis in gastric cancer: Strategies and opportunities

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 228 - 245

Published: Oct. 30, 2023

Summary Ferroptosis is a novel form of programmed cell death morphologically, genetically, and biochemically distinct from other pathways characterized by the accumulation iron‐dependent lipid peroxides oxidative damage. It now understood that ferroptosis plays an essential role in various biological processes, especially metabolism iron, lipids, amino acids. Gastric cancer (GC) prevalent malignant tumor worldwide with low early diagnosis rates high metastasis rates, accounting for its relatively poor prognosis. Although chemotherapy commonly used to treat GC, drug resistance often leads therapeutic outcomes. In last several years, extensive research on has highlighted significant potential GC therapy, providing promising strategy address associated standard therapies. this review, we offer summary key regulatory factors related mechanisms underlying ferroptosis. Various inducers inhibitors specifically targeting are uncovered. Additionally, explore prospective applications outcomes these agents field emphasizing their capacity improve patient population.

Language: Английский

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NFE2L2 and ferroptosis resistance in cancer therapy

Cancer Drug Resistance, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

NFE2-like basic leucine zipper transcription factor 2 (NFE2L2, also known as NRF2), is a key in the cellular defense against oxidative stress, playing crucial role cancer cell survival and resistance to therapies. This review outlines current knowledge on link between NFE2L2 ferroptosis - form of regulated death characterized by iron-dependent lipid peroxidation within cells. While activation can protect normal cells from damage, its overexpression contributes drug upregulating antioxidant defenses inhibiting ferroptosis. We delve into molecular pathways ferroptosis, highlighting involvement target genes, such

Language: Английский

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