Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Dec. 8, 2022

Abstract Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various activities, including clearance aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target development cancer medications recent years. However, because tumor show avoidance apoptosis, which causes treatment resistance recurrence, numerous studies been devoted alternative mortality processes, namely necroptosis, pyroptosis, ferroptosis, cuproptosis; these modalities extensively studied shown be crucial therapy effectiveness. Furthermore, evidence suggests that undergoing may alter immunogenicity microenvironment (TME) some extent, rendering it more suitable inhibiting progression metastasis. In addition, other components TME undergo abovementioned forms induce immune attacks on cells, resulting enhanced antitumor responses. Hence, this review discusses molecular processes features cuproptosis effects novel proliferation Importantly, introduces complex affect biology. It also summarizes potential agents nanoparticles or inhibit their therapeutic based from vivo vitro reports clinical trials inducers evaluated treatments patients. Lastly, we summarized impact modulating drug advantages adding modulators over conventional treatments.

Language: Английский

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Carbon Quantum Dots-Based Nanozyme from Coffee Induces Cancer Cell Ferroptosis to Activate Antitumor Immunity

ACS Nano, Journal Year: 2022, Volume and Issue: 16(6), P. 9228 - 9239

Published: May 27, 2022

Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared natural enzymes. Thus, discovery of CQDs-based nanozymes with low toxicity from resources, especially daily food, implies a promising direction for exploring treatment strategies human diseases. Here, we report biocompatible nanozyme prepared chlorogenic acid (ChA), major bioactive product coffee. We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation GPX4-catalyzed lipid repair systems. In vivo, dramatically suppressed the tumor growth in HepG2-tumor-bearing mice negligible side toxicity. Particularly, hepatoma H22-bearing mice, recruited massive tumor-infiltrating immune cells including T cells, NK macrophages, thereby converting "cold" "hot" tumors activating systemic antitumor responses. Taken together, our study suggests product-derived coffee can serve biologically safe anticancer therapeutics may aid development nanotechnology-based immunotherapeutic.

Language: Английский

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Functional states of myeloid cells in cancer

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 490 - 504

Published: March 1, 2023

Language: Английский

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Ferroptosis: a double-edged sword mediating immune tolerance of cancer

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(11)

Published: Nov. 5, 2022

Abstract The term ferroptosis was put forward in 2012 and has been researched exponentially over the past few years. Ferroptosis is an unconventional pattern of iron-dependent programmed cell death, which belongs to a type necrosis distinguished from apoptosis autophagy. Actuated by phospholipid peroxidation, modulated various cellular metabolic signaling pathways, including amino acid, lipid, iron, mitochondrial metabolism. Notably, associated with numerous diseases plays double-edged sword role. Particularly, metastasis-prone or highly-mutated tumor cells are sensitive ferroptosis. Hence, inducing prohibiting vastly promising potential treating drug-resistant cancers. Immunotolerant cancer not traditional death pathway such as necroptosis, while crucial role mediating immune antagonize tolerance, broad prospects clinical setting. Herein, we summarized mechanisms delineated regulatory network ferroptosis, emphasized its dual proposed significant benefits microenvironment, ultimately presented some provocative doubts. This review aims provide practical guidelines research directions for practice immune-resistant tumors.

Language: Английский

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Intermittent dietary methionine deprivation facilitates tumoral ferroptosis and synergizes with checkpoint blockade

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 8, 2023

Dietary methionine interventions are beneficial to apoptosis-inducing chemotherapy and radiotherapy for cancer, while their effects on ferroptosis-targeting therapy immunotherapy unknown. Here we show the length of time deprivation affects tumoral ferroptosis differently. Prolonged prevents glutathione (GSH) depletion from exceeding death threshold by blocking cation transport regulator homolog 1 (CHAC1) protein synthesis. Whereas, short-term starvation accelerates stimulating CHAC1 transcription. In vivo, dietary with intermittent but not sustained augments ferroptosis. Intermittent also sensitizes tumor cells against CD8+ T cell-mediated cytotoxicity synergize checkpoint blockade upregulation. Clinically, correlates clinical benefits improved survival in cancer patients treated blockades. Lastly, triple combination deprivation, system xc- inhibitor PD-1 shows superior antitumor efficacy. Thus, is a promising regimen target augment immunotherapy.

Language: 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, Journal Year: 2023, Volume and Issue: 10(20)

Published: May 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.

Language: Английский

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Ferroptosis and Senescence: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3658 - 3658

Published: Feb. 11, 2023

Senescence is a cellular aging process in all multicellular organisms. It characterized by decay functions and proliferation, resulting increased damage death. This condition plays an essential role the significantly contributes to development of age-related complications. On other hand, ferroptosis systemic cell death pathway excessive iron accumulation followed generation reactive oxygen species (ROS). Oxidative stress common trigger this may be induced various factors such as toxins, drugs, inflammation. Ferroptosis linked numerous disorders, including cardiovascular disease, neurodegeneration, cancer. believed contribute tissue organ occurring with aging. has also been pathologies, diseases, diabetes, In particular, senescent cells have shown produce inflammatory cytokines pro-inflammatory molecules that can these conditions. turn, health known play pathologies promoting damaged or diseased contributing inflammation often associated. Both senescence are complex pathways still not fully understood. Further research needed thoroughly investigate processes identify potential interventions target order prevent treat systematic review aims assess mechanisms underlying link connecting senescence, ferroptosis, aging, whether they exploited block limit physiological elderly people for healthy longevity.

Language: Английский

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Trial watch: chemotherapy-induced immunogenic cell death in oncology

OncoImmunology, Journal Year: 2023, Volume and Issue: 12(1)

Published: June 3, 2023

Immunogenic cell death (ICD) refers to an immunologically distinct process of regulated that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency ICD is dependent on the immunogenicity cells as defined by antigenicity these their ability expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) cytokines type I interferons (IFNs). Moreover, it crucial host’s system can adequately detect adjuvanticity Over years, several well-known chemotherapies have been validated potent inducers, including (but not limited to) anthracyclines, paclitaxels, oxaliplatin. ICD-inducing chemotherapeutic drugs serve important combinatorial partners for anti-cancer immunotherapies highly immuno-resistant tumors. In this Trial Watch, we describe current trends in preclinical clinical integration chemotherapy existing immuno-oncological paradigms.

Language: Английский

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Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases

Archives of Toxicology, Journal Year: 2024, Volume and Issue: 98(3), P. 579 - 615

Published: Jan. 24, 2024

Abstract This article provides an overview of the background knowledge ferroptosis in nervous system, as well key role nuclear factor E2-related 2 (Nrf2) regulating ferroptosis. The takes Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD), and amyotrophic lateral sclerosis (ALS) starting point to explore close association between Nrf2 ferroptosis, which is clear significant importance for understanding mechanism neurodegenerative diseases (NDs) based on oxidative stress (OS). Accumulating evidence links pathogenesis NDs. As progresses, damage antioxidant excessive OS, altered expression levels, especially inhibition by lipid peroxidation inhibitors adaptive enhancement signaling, demonstrate potential clinical significance detecting identifying targeted therapy neuronal loss mitochondrial dysfunction. These findings provide new insights possibilities treatment prevention

Language: Английский

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RSL3 induces ferroptosis by activating the NF-κB signalling pathway to enhance the chemosensitivity of triple-negative breast cancer cells to paclitaxel

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 11, 2025

Chemotherapy resistance in triple-negative breast cancer (TNBC) leads to poor therapeutic effects and a prognosis. Given that paclitaxel-based chemotherapy is the main treatment method for TNBC, enhancing its chemosensitivity has been research focus. Induced ferroptosis of tumour cells proven increase chemosensitivity, but ability sensitize TNBC paclitaxel (PTX) unknown. In our experiments, measurements viability proliferation validated synergistic effect PTX combined with RSL3 on cells. The accumulation intracellular Fe2+ lipid reactive oxygen species, as well expression malondialdehyde, illustrated enhanced by inducing ferroptosis. Through transcriptome sequencing, series differentially expressed genes were identified, which cytokines, such CXCLs, was significantly increased group, combination therapy enriched mainly NFκB signalling pathway. subsequent validation use NF-κB inhibitor BAY11-7082 reversed inhibitory cell activity. xenograft immunodeficient mouse model, vivo further verified. Our both vitro, activating pathway, thereby increasing PTX. This study provides new insights improving efficacy strategies.

Language: Английский

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