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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Selective Targeting of Cancer Cells by Copper Ionophores: An Overview

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: March 4, 2022

Conventional cancer therapies suffer from severe off-target effects because most of them target critical facets cells that are generally shared by all rapidly proliferating cells. The development new therapeutic agents should aim to increase selectivity and therefore reduce side effects. In addition, these overcome cell resistance stem Some copper ionophores have shown promise in this direction thanks an intrinsic preferentially inducing cuproptosis compared normal Here, Cu discussed with a focus on towards the mechanisms responsible for selectivity. proposed strategies, further improve targeting ionophores, also reported.

Language: Английский

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Copper-Induced Tumor Cell Death Mechanisms and Antitumor Theragnostic Applications of Copper Complexes

Nanomedicine, Journal Year: 2022, Volume and Issue: 17(5), P. 303 - 324

Published: Jan. 21, 2022

Recent studies found that unbalanced copper homeostasis affect tumor growth, causing irreversible damage. Copper can induce multiple forms of cell death, including apoptosis and autophagy, through various mechanisms, reactive oxygen species accumulation, proteasome inhibition, antiangiogenesis. Hence, in vivo has attracted tremendous attention is the research spotlight field treatment. This review first highlights three typical copper's antitumor mechanisms. Then, development diverse biomaterials nanotechnology allowing to be fabricated into structures realize its theragnostic action discussed. Novel complexes their clinical applications are subsequently described.

Language: Английский

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Prognostic analysis of cuproptosis-related gene in triple-negative breast cancer

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 1, 2022

Cuproptosis is a copper-dependent cell death mechanism that associated with tumor progression, prognosis, and immune response. However, the potential role of cuproptosis-related genes (CRGs) in microenvironment (TME) triple-negative breast cancer (TNBC) remains unclear.In total, 346 TNBC samples were collected from The Cancer Genome Atlas database three Gene Expression Omnibus datasets, classified using R software packages. relationships between different subgroups clinical pathological characteristics, infiltration mutation status TME examined. Finally, nomogram calibration curve constructed to predict patient survival probability improve applicability CRG_score.We identified two CRG clusters characteristics highly consistent those immune-inflamed immune-desert clusters. Furthermore, we demonstrated gene signature can be used evaluate infiltration, features, prognostic status. Low CRG_scores characterized by high burden activation, good probability, more immunoreactivity CTLA4, while activation stromal pathways immunosuppression.This study revealed effects CRGs on TME, clinicopathological prognosis TNBC. closely immunity are tool for predicting prognosis. Our data provide new directions development novel drugs future.

Language: Английский

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Cuproptosis-Associated lncRNA Establishes New Prognostic Profile and Predicts Immunotherapy Response in Clear Cell Renal Cell Carcinoma

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: July 15, 2022

Background: Clear cell renal carcinoma (ccRCC) accounts for 80% of all kidney cancers and has a poor prognosis. Recent studies have shown that copper-dependent, regulated death differs from previously known mechanisms (apoptosis, ferroptosis, necroptosis) is dependent on mitochondrial respiration (Tsvetkov et al., Science, 2022, 375 (6586), 1254-1261). Studies also suggested targeting cuproptosis may be novel therapeutic strategy cancer therapy. In ccRCC, both lncRNA were critical, but the not fully understood. The aim our study was to construct prognostic profile based cuproptosis-associated lncRNAs predict prognosis ccRCC immune clear (ccRCC). Methods: We downloaded transcriptional clinical information Cancer Genome Atlas (TCGA). Co-expression network analysis, Cox regression method, least absolute shrinkage selection operator (LASSO) method used identify risk model. addition, predictive performance model validated recognized by an integrated approach. then constructed nomogram patients. Differences in biological function investigated GO, KEGG, immunoassay. Immunotherapy response measured using tumor mutational burden (TMB) dysfunction rejection (TIDE) scores. Results: panel 10 (HHLA3, H1-10-AS1, PICSAR, LINC02027, SNHG15, SNHG8, LINC00471, EIF1B-AS1, LINC02154, MINCR) prediction Kaplan-Meier ROC curves showed feature had acceptable validity TCGA training, test, complete groups. higher diagnostic efficiency compared other features. analysis Immune infiltration ssGSEA further confirmed features significantly associated with status Notably, superimposed effect patients high-risk group high TMB resulted shorter survival. TIDE scores poorer outcome checkpoint blockade these Conclusion: ten cuproptosis-related profiles help assess molecular improve treatment options, which can applied clinic.

Language: Английский

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Potential of Copper and Copper Compounds for Anticancer Applications

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(2), P. 234 - 234

Published: Feb. 3, 2023

Inducing cancer cell death has always been a research hotspot in life sciences. With the continuous deepening and diversification of related research, potential value metal elements inducing explored. Taking iron as an example, ferroptosis, mainly characterized by increasing load driving production large amounts lipid peroxides eventually leading to death, recently attracted great interest community. After iron, copper, trace element, received extensive attention especially tumor death. Copper its complexes can induce autophagy or apoptosis cells through variety different mechanisms action (activation stress pathways, arrest cycle, inhibition angiogenesis, cuproptosis, paraptosis), which are promising therapy have become new hotspots treatment research. This article reviews main applications novel copper compound-induced focusing on compounds their anticancer applications.

Language: Английский

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A review on metal complexes and its anti-cancer activities: Recent updates from in vivo studies

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116211 - 116211

Published: Jan. 29, 2024

Research into cancer therapeutics has uncovered various potential medications based on metal-containing scaffolds after the discovery and clinical applications of cisplatin as an anti-cancer agent. This resulted in many metallodrugs that can be put medical applications. These have a wider variety functions mechanisms action than pure organic molecules. Although platinum-based medicines are very efficient agents, they often accompanied by significant side effects toxicity limited resistance. Some most studied developed alternatives to include ruthenium, gold, copper, iridium, osmium, which showed effectiveness against cell lines. metal-based represent exciting new category treatments sparked renewed interest search for effective therapies. Despite widespread development metal complexes touted powerful promising vitro therapeutics, only small percentage these compounds shown their worth vivo models. Metallodrugs, more less toxic drugs treat drug-resistant cells, focus this review. Here, we highlighted some recently Pt, Ru, Au, Cu, Ir, Os antitumor properties between 2017 2023.

Language: Английский

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Copper in cancer: From pathogenesis to therapy

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114791 - 114791

Published: April 25, 2023

One of the basic trace elements for structure and metabolism human tissue is copper. However, as a heavy metal, excessive intake or abnormal accumulation copper in body can cause inevitable damage to organism because result direct injury various cell components disruption redox balance, eventually leading death. Interestingly, growing research reports that diverse cancers have raised serum tumor levels. Tumor cells depend on more their than normal cells, decrease overload detrimental effect cells. New modalities identifying characterizing copper-dependent signals offer translational opportunities therapy, but mechanisms remain unclear. Therefore, this article summarizes what we currently know about correlation between cancer describes characteristics prospective application copper-derived therapeutics.

Language: Английский

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Riding the metal wave: A review of the latest developments in metal-based anticancer agents

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 501, P. 215579 - 215579

Published: Nov. 28, 2023

Language: Английский

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Nanoparticles Synergize Ferroptosis and Cuproptosis to Potentiate Cancer Immunotherapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: March 13, 2024

Abstract The recent discovery of copper‐mediated and mitochondrion‐dependent cuproptosis has aroused strong interest in harnessing this novel mechanism cell death for cancer therapy. Here the design a core‐shell nanoparticle, CuP/Er, co‐delivery copper (Cu) erastin (Er) to cells synergistic ferroptosis is reported. anti‐Warburg effect Er sensitizes tumor Cu‐mediated cuproptosis, leading irreparable mitochondrial damage by depleting glutathione enhancing lipid peroxidation. CuP/Er induces immunogenic death, enhances antigen presentation, upregulates programmed death‐ligand 1 expression. Consequently, promotes proliferation infiltration T cells, when combined with immune checkpoint blockade, effectively reinvigorates mediate regression murine colon adenocarcinoma triple‐negative breast prevent metastasis. This study suggests unique opportunity synergize combination therapy nanoparticles elicit antitumor effects potentiate current immunotherapies.

Language: Английский

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