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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Targeting p53 pathways: mechanisms, structures and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 1, 2023

The TP53 tumor suppressor is the most frequently altered gene in human cancers, and has been a major focus of oncology research. p53 protein transcription factor that can activate expression multiple target genes plays critical roles regulating cell cycle, apoptosis, genomic stability, widely regarded as "guardian genome". Accumulating evidence shown also regulates metabolism, ferroptosis, microenvironment, autophagy so on, all which contribute to suppression. Mutations not only impair its function, but confer oncogenic properties mutants. Since mutated inactivated malignant tumors, it very attractive for developing new anti-cancer drugs. However, until recently, was considered an "undruggable" little progress made with p53-targeted therapies. Here, we provide systematic review diverse molecular mechanisms signaling pathway how mutations impact progression. We discuss key structural features inactivation by mutations. In addition, efforts have therapies, challenges encountered clinical development.

Language: Английский

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Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Sept. 26, 2022

Abstract The clinical responses observed following treatment with immune checkpoint inhibitors (ICIs) support immunotherapy as a potential anticancer treatment. However, large proportion of patients cannot benefit from it due to resistance or relapse, which is most likely attributable the multiple immunosuppressive cells in tumor microenvironment (TME). Myeloid-derived suppressor (MDSCs), heterogeneous array pathologically activated immature cells, are chief component networks. These potently suppress T-cell activity and thus contribute escape malignant tumors. New findings indicate that targeting MDSCs might be an alternative promising target for immunotherapy, reshaping enhancing efficacy cancer immunotherapy. In this review, we focus primarily on classification inhibitory function crosstalk between other myeloid cells. We also briefly summarize latest approaches therapies MDSCs.

Language: Английский

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Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend?

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Sept. 26, 2022

The major concept of "oxidative stress" is an excess elevated level reactive oxygen species (ROS) which are generated from vigorous metabolism and consumption oxygen. precise harmonization oxidative stresses between mitochondria other organelles in the cell absolutely vital to survival. Under stress, ROS produced mediator for tumorigenesis different aspects, such as proliferation, migration/invasion, angiogenesis, inflammation, immunoescape allow cancer cells adapt rigorous environment. Accordingly, dynamic balance not only orchestrate complex signaling events but also affect components tumor microenvironment (TME). Immune cells, M2 macrophages, dendritic T immunosuppressive TME ROS-induced inflammation. Based on this notion, numerous strategies mitigate tumors have been tested prevention or therapies; however, these manipulations devised sources mechanisms without established effectiveness. Herein, we integrate current progress regarding impact mitochondrial TME, immune discuss combination emerging ROS-modulating with immunotherapies achieve antitumor effects.

Language: Английский

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Stimuli-activatable nanomedicine meets cancer theranostics

Theranostics, Journal Year: 2023, Volume and Issue: 13(15), P. 5386 - 5417

Published: Jan. 1, 2023

Stimuli-activatable strategies prevail in the design of nanomedicine for cancer theranostics.Upon exposure to endogenous/exogenous stimuli, stimuli-activatable could be self-assembled, disassembled, or functionally activated improve its biosafety and diagnostic/therapeutic potency.A myriad tumor-specific features, including a low pH, high redox level, overexpressed enzymes, along with exogenous physical stimulation sources (light, ultrasound, magnet, radiation) have been considered nano-medicinal products.Recently, novel stimuli explored elegant designs emerged nanomedicine.In addition, multi-functional theranostic has employed imaging-guided image-assisted antitumor therapy.In this review, we rationalize development clinical pressing needs.Stimuli-activatable self-assembly, disassembly functional activation approaches developing realize better efficacy are elaborated state-of-the-art advances their structural detailed.A reflection, status, future perspectives provided.

Language: Английский

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SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells

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

Published: June 21, 2023

The cystine transporter solute carrier family 7 member 11 (SLC7A11; also called xCT) protects cancer cells from oxidative stress and is overexpressed in many cancers. Here we report a surprising finding that, whereas moderate overexpression of SLC7A11 beneficial for treated with H2O2, common inducer, its high dramatically increases H2O2-induced cell death. Mechanistically, uptake combination H2O2 treatment results toxic buildup intracellular other disulfide molecules, NADPH depletion, redox system collapse, rapid death (likely disulfidptosis). We further show that promotes tumor growth but suppresses metastasis, likely because metastasizing expression are particularly susceptible to stress. Our findings reveal level dictates cells' sensitivity suggests context-dependent role biology.

Language: Английский

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STAT proteins in cancer: orchestration of metabolism

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(3), P. 115 - 134

Published: Jan. 3, 2023

Language: Английский

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Theranostic Fluorescent Probes

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(5), P. 2699 - 2804

Published: Feb. 29, 2024

The ability to gain spatiotemporal information, and in some cases achieve control, the context of drug delivery makes theranostic fluorescent probes an attractive intensely investigated research topic. This interest is reflected steep rise publications on topic that have appeared over past decade. Theranostic probes, their various incarnations, generally comprise a fluorophore linked masked drug, which released as result certain stimuli, with both intrinsic extrinsic stimuli being reported. release then signaled by emergence signal. Importantly, use appropriate fluorophores has enabled not only this emerging fluorescence marker for but also provided modalities useful photodynamic, photothermal, sonodynamic therapeutic applications. In review we highlight recent work particular focus are activated tumor microenvironments. We summarize efforts develop other applications, such neurodegenerative diseases antibacterials. celebrates diversity designs reported date, from discrete small-molecule systems nanomaterials. Our aim provide insights into potential clinical impact still-emerging direction.

Language: Английский

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The Current Status of Photodynamic Therapy in Cancer Treatment

Cancers, Journal Year: 2023, Volume and Issue: 15(3), P. 585 - 585

Published: Jan. 18, 2023

Although we have made great strides in treating deadly diseases over the years, cancer therapy still remains a daunting challenge. Among numerous anticancer methods, photodynamic (PDT), non-invasive therapeutic approach, has attracted much attention. PDT exhibits outstanding performance therapy, but some unavoidable disadvantages, including limited light penetration depth, poor tumor selectivity, as well oxygen dependence, largely limit its efficiency for solid tumors treatment. Thus, strategies gone into overcoming these obstacles, such exploring new photosensitizers with higher conversion efficiency, alleviating hypoxia to fuel generation of reactive species (ROS), designing tumor-targeted PS, and applying PDT-based combination strategies. In this review, briefly summarized related approaches, which are mainly characterized by advanced PSs, PSs excellent additional refreshing features. We also summarize therapies effects.

Language: Английский

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Stimuli-responsive ferroptosis for cancer therapy

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(12), P. 3955 - 3972

Published: Jan. 1, 2023

This review highlights recent advances in the utilization of various endogenous and exogenous stimuli to activate nanocarrier-based ferroptosis cancer therapy that can be effective treating conventional drug-resistant tumors.

Language: Английский

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