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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Unraveling tumor microenvironment of small-cell lung cancer: Implications for immunotherapy

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 117 - 125

Published: Sept. 29, 2022

Language: Английский

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PANoptosis: Mechanisms, biology, and role in disease

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 246 - 262

Published: Oct. 12, 2023

Summary Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which mediated by multifaceted PANoptosome complexes assembled via integrating components from other modalities. There growing interest in process function of PANoptosis. Accumulating evidence suggests that occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, cancer. Given impact across disease spectrum, this review briefly describes relationships highlights key molecules formation activation, outlines roles diseases together with potential therapeutic targeting. We also discuss important concepts pressing issues future research. Improved understanding its mechanisms crucial identifying novel targets strategies.

Language: Английский

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Small cell lung cancer: Novel treatments beyond immunotherapy

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 376 - 385

Published: May 11, 2022

Small cell lung cancer (SCLC) arises in peribronchial locations and infiltrates the bronchial submucosa, including about 15% of cases. Despite decades research, prognosis for SCLC patients remains poor because this tumor is characterized by an exceptionally high proliferative rate, strong tendency early widespread metastasis acquired chemoresistance. Omics profiling revealed that harbor extensive chromosomal rearrangements a very mutation burden. This led to development immune-checkpoint inhibitors as single agents or combination with chemotherapy, which however resulted prolonged benefit only small subset patients. Thus, present review discusses rationale limitations immunotherapeutic approaches, presenting current biological understanding aberrant signaling pathways might be exploited new potential treatments. In particular, targeting DNA damage repair, cycle checkpoint, apoptosis showed several promising results different preclinical models. Epigenetic alterations, gene amplifications mutations can act biomarkers context. Future research improved clinical outcome will depend on integration between these omics pharmacological studies translational order identify specific predictive hopefully validated using trials biomarker-selected targeted

Language: Английский

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Immuno-photodynamic Therapy (IPDT): Organic Photosensitizers and Their Application in Cancer Ablation

JACS Au, Journal Year: 2023, Volume and Issue: 3(3), P. 682 - 699

Published: Feb. 14, 2023

Photosensitizer-based photodynamic therapy (PDT) has been considered as a promising modality for fighting diverse types of cancers. PDT directly inhibits local tumors by minimally invasive strategy, but it seems to be incapable achieving complete eradication and fails prevent metastasis recurrence. Recently, increasing events proved that was associated with immunotherapy triggering immunogenic cell death (ICD). Upon specific wavelength light irradiation, the photosensitizers will turn surrounding oxygen molecules into cytotoxic reactive species (ROS) killing cancer cells. Simultaneously, dying tumor cells release tumor-associated antigens, which could improve immunogenicity activate immune However, progressively enhanced immunity is typically limited intrinsic immunosuppressive microenvironment (TME). To overcome this obstacle, immuno-photodynamic (IPDT) come one most beneficial strategies, takes advantage stimulate response unite inducing immune-OFF immune-ON ones, achieve systemic In Perspective, we provide review recent advances in organic photosensitizer-based IPDT. The general process responses triggered (PSs) how enhance antitumor pathway modifying chemical structure or conjugating targeting component discussed. addition, future perspectives challenges IPDT strategies are also We hope Perspective inspire more innovative ideas executable developments war against cancer.

Language: Английский

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Application of artificial intelligence for improving early detection and prediction of therapeutic outcomes for gastric cancer in the era of precision oncology

Seminars in Cancer Biology, Journal Year: 2023, Volume and Issue: 93, P. 83 - 96

Published: April 27, 2023

Language: Английский

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High Immunogenic Cuproptosis Evoked by In Situ Sulfidation‐Activated Pyroptosis for Tumor‐Targeted Immunotherapy of Colorectal Cancer

Small Science, Journal Year: 2024, Volume and Issue: 4(3)

Published: Jan. 17, 2024

Despite the great potential of cuproptosis in tumor therapy, current cuproptosis‐based therapy still suffers from compromised efficiency immune activation. Pyroptosis, a proinflammatory cell death modality, provides good opportunity to induce immunogenic (ICD) and promote systemic response. However, synergistic pyroptosis has not been fully explored. Herein, it is discovered that Cu(II)‐based metal–organic framework (MOF) nanoparticles (NPs) can synergistically evoke ICD for high‐efficiency tumor‐targeted immunotherapy. Although MOF‐199 widely used immunogenicity unclear. Pluronic F127‐modified NPs ( F127 NPs) show dual‐responsiveness glutathione (GSH) hydrogen sulfide (H 2 S). Once entering cancer cells, dissociate GSH‐enriched microenvironment (TME) release copper ion copper‐overload‐mediated cuproptosis. Meanwhile, transform Cu 2− x S by situ sulfidation under H S‐enriched colorectal (CRC) TME. Under photothermal chemodynamic (PTT/CDT) NPs, caspase‐3 activated gasdermin E (GSDME)‐related triggered. The have proved superior antitumor immunity effect both vitro vivo experiments. This work new strategy achieve immunotherapy with high simple NPs.

Language: Английский

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Reshaping the immune microenvironment and reversing immunosenescence by natural products: prospects for immunotherapy in gastric cancer

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: 110, P. 1 - 16

Published: Feb. 8, 2025

Language: Английский

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Targeting ferroptosis as a vulnerability in pulmonary diseases

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(7)

Published: July 26, 2022

Abstract Ferroptosis is an iron-dependent regulated cell death marked by excessive oxidative phospholipids (PLs). The polyunsaturated fatty acids-containing (PUFA-PLs) are highly susceptible to lipid peroxidation under stress. Numerous pulmonary diseases occurrences and degenerative pathologies driven ferroptosis. This review discusses the role of ferroptosis in pathogenesis including asthma, lung injury, cancer, fibrotic diseases, infection. Additionally, it proposed that targeting a potential treatment for particularly drug-resistant cancer or antibiotic-resistant infection, reduces treatment-related adverse events.

Language: Английский

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The role of stem cells in small-cell lung cancer: Evidence from chemoresistance to immunotherapy

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 87, P. 160 - 169

Published: Nov. 9, 2022

Small cell lung cancer (SCLC) is the most aggressive subtype of cancer, accounting for approximately 15 % among all cancers. Despite ability chemotherapy, first-line treatment SCLC, to rapidly shrink tumors, nearly patients experience recurrence and metastasis within a few months. Cancer stem cells (CSCs) are small population tumor responsible tumorigenesis, metastasis, after treatment, which play crucial role in chemoresistance by promoting DNA repair expression drug resistance-associated proteins. Thus, targeting CSCs has been successful certain malignancies. Tumor therapy entered era immunotherapy numerous preclinical trials have demonstrated effectiveness immunotherapeutic approaches CSCs, such as vaccines chimeric antigen receptor (CAR) T cell, feasibility combining them with chemotherapy. Therefore, deeper understanding interaction between immune system essential facilitate advances new immunotherapies well combination standard drugs This narrative review summarizes mechanisms SCLC latest targeted therapies. Thereafter, we discuss effects on microenvironment corresponding approaches. Eventually, propose that promising direction

Language: Английский

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