Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: June 20, 2022

Abstract In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not ICIs, partly caused absence of tumor-infiltrating lymphocytes (TILs), significantly limits application ICIs. Converting these “cold” into “hot” may ICIs is an unsolved question immunotherapy. Since it a general characteristic cancers resist apoptosis, induction non-apoptotic regulated cell death (RCD) emerging as new treatment strategy. Recently, several studies have revealed interaction between RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, necroptosis exhibit synergistic responses while possibly exerting inhibitory effects on responses. Thus, targeted therapies (inducers inhibitors) against combination with exert potent activity, resistant This review summarizes multilevel relationship immunity RCD, including necroptosis, potential targeting improve efficacy malignancy.

Language: Английский

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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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Copper-dependent autophagic degradation of GPX4 drives ferroptosis

Autophagy, Journal Year: 2023, Volume and Issue: 19(7), P. 1982 - 1996

Published: Jan. 9, 2023

Ferroptosis is a type of iron-dependent regulated cell death characterized by unrestricted lipid peroxidation and membrane damage. Although GPX4 (glutathione peroxidase 4) plays master role in blocking ferroptosis eliminating phospholipid hydroperoxides, the regulation remains poorly understood. Here, we report an unexpected for copper promoting ferroptotic death, but not cuproptosis, inducing macroautophagic/autophagic degradation GPX4. Copper chelators reduce sensitivity do inhibit other types such as apoptosis, necroptosis, alkaliptosis. Conversely, exogenous increases ubiquitination formation aggregates directly binding to protein cysteines C107 C148. TAX1BP1 (Tax1 1) then acts autophagic receptor subsequent response stress. Consequently, enhances ferroptosis-mediated tumor suppression mouse model pancreatic cancer tumor, whereas attenuate experimental acute pancreatitis associated with ferroptosis. Taken together, these findings provide new insights into link between metal stress autophagy-dependent death.Abbreviations: CALCOCO2, calcium coiled-coil domain 2; GPX4, glutathione 4; MAP1LC3A/B, microtubule 1 light chain 3 alpha/beta; MPO, myeloperoxidase; NCOA4, nuclear coactivator OPTN, optineurin; PDAC, ductal adenocarcinoma; RIPK1, interacting serine/threonine kinase 1; ROS, reactive oxygen species; SLC40A1, solute carrier family 40 member SQSTM1, sequestosome TAX1BP1, Tax1 TEPA, tetraethylenepentamine; TM, tetrathiomolybdate.

Language: Английский

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Copper metabolism in cell death and autophagy

Autophagy, Journal Year: 2023, Volume and Issue: 19(8), P. 2175 - 2195

Published: April 14, 2023

Copper is an essential trace element in biological systems, maintaining the activity of enzymes and function transcription factors. However, at high concentrations, copper ions show increased toxicity by inducing regulated cell death, such as apoptosis, paraptosis, pyroptosis, ferroptosis, cuproptosis. Furthermore, can trigger macroautophagy/autophagy, a lysosome-dependent degradation pathway that plays dual role regulating survival or death fate cells under various stress conditions. Pathologically, impaired metabolism due to environmental genetic causes implicated variety human diseases, rare Wilson disease common cancers. Therapeutically, copper-based compounds are potential chemotherapeutic agents be used alone combination with other drugs approaches treat cancer. Here, we review progress made understanding metabolic processes their impact on regulation autophagy. This knowledge may help design future clinical tools improve cancer diagnosis treatment.

Language: Английский

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Apoptotic cell death in disease—Current understanding of the NCCD 2023

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(5), P. 1097 - 1154

Published: April 26, 2023

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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Overcoming cancer chemotherapy resistance by the induction of ferroptosis

Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 66, P. 100916 - 100916

Published: Dec. 29, 2022

Language: Английский

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Photon-Controlled Pyroptosis Activation (PhotoPyro): An Emerging Trigger for Antitumor Immune Response

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(11), P. 6007 - 6023

Published: March 7, 2023

Pyroptosis refers to the process of gasdermin-mediated lytic programmed cell death (PCD) characterized by release pro-inflammatory cytokines. Our knowledge pyroptosis has expanded beyond cellular level and now includes extracellular responses. In recent years, attracted considerable attention due its potential induce host immunity. For instance, at 2022 International Medicinal Chemistry Natural Active Ligand Metal-Based Drugs (MCNALMD) conference, numerous researchers demonstrated an interest in photon-controlled activation ("PhotoPyro"), emerging pyroptosis-engineered approach for activating systemic immunity via photoirradiation. Given this enthusiasm, we share Perspective our views on area expound how why "PhotoPyro" could trigger antitumor (i.e., turning so-called "cold" tumors "hot"). doing so, have tried highlight cutting-edge breakthroughs PhotoPyro while suggesting areas future contributions. By providing insights into current state art serving as a resource individuals interested working area, it is hoped that will set stage evolve broadly applicable cancer treatment strategy.

Language: Английский

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Iron and copper: critical executioners of ferroptosis, cuproptosis and other forms of cell death

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 16, 2023

Abstract Regulated cell death (RCD) is a regulable that involves well-organized signaling cascades and molecular mechanisms. RCD implicated in fundamental processes such as organ production tissue remodeling, removing superfluous structures or cells, regulating numbers. Previous studies have not been able to reveal the complete mechanisms, novel methods of are constantly being proposed. Two metal ions, iron (Fe) copper (Cu) essential factors leading RCDs only induce ferroptosis cuproptosis, respectively but also lead impairment eventually diverse death. This review summarizes direct indirect mechanisms by which Fe Cu impede growth various forms mediated these two metals. Moreover, we aimed delineate interrelationships between with distinct pathways shedding light on complex intricate govern cellular survival Finally, prospects outlined this suggest approach for investigating death, may involve integrating current therapeutic strategies offer promising solution overcome drug resistance certain diseases.

Language: Английский

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Unravelling the enigma of siRNA and aptamer mediated therapies against pancreatic cancer

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Jan. 12, 2023

Pancreatic cancer (PC) is a fatal disease that has poor 5-year survival rate. The prognosis can be attributed to both troublesome detections at the initial stage, which makes majority of treatment options largely unsuccessful and leads extensive metastasis, as well its distinct pathophysiological characteristics, such rich desmoplastic tumours bounded by dysplastic hypo perfused vessels restricting mobility therapeutic agents. Continued attempts have been made utilise innovative measures for battling PC increase effectiveness therapies overcome their cytotoxicity. Combined targeting gene silencing approach shown improved outcomes in patients' rates quality life, offering potential solution complications. It particularly targets various barriers alleviate delivery problems diminish tumour recurrence metastasis. While aptamers, type single-stranded nucleic acids with strong binding affinity specificity target molecules, recently surfaced viable strategy, siRNA interfere expression certain genes. By concurrently suppressing genes boosting targeted approach, cocktail siRNA/Aptamer other drugs circumvent multi-drug resistance phenomena. Additionally, combination therapy additive or synergistic effects considerably efficacy anti-cancer medications. This study outlines primary difficulties treating PC, along recent developments mediated drug solve major hiccup oncology field.

Language: Английский

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