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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Adverse clinical outcomes and immunosuppressive microenvironment of RHO-GTPase activation pattern in hepatocellular carcinoma

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 31, 2024

Abstract Background Emerging evidence suggests that Rho GTPases play a crucial role in tumorigenesis and metastasis, but their involvement the tumor microenvironment (TME) prognosis of hepatocellular carcinoma (HCC) is not well understood. Methods We aim to develop prediction system called GTPases-related gene score (RGPRG score) using GTPase signaling genes further bioinformatic analyses. Results Our work found HCC patients with high RGPRG had significantly worse survival increased immunosuppressive cell fractions compared those low score. Single-cell cohort analysis revealed an immune-active TME score, strengthened communication from T/NK cells other through MIF networks. Targeting these alterations TME, have immunotherapeutic outcomes decreased time immunotherapy cohort. Moreover, was be correlated 27 cancers. In vitro experiments confirmed knockdown key GTPase-signaling biomarker SFN inhibited proliferation, invasion, migration. Conclusions This study provides new insight into features clinical use pattern at bulk-seq single-cell level, which may contribute guiding personalized treatment improving outcome HCC.

Language: Английский

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Nanomaterials for Disease Treatment by Modulating the Pyroptosis Pathway

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 13(1)

Published: June 25, 2023

Pyroptosis differs significantly from apoptosis and cell necrosis as an alternative mode of programmed death. Its occurrence is mediated by the gasdermin protein, leading to characteristic outcomes including swelling, membrane perforation, release contents. Research underscores role pyroptosis in etiology progression many diseases, making it a focus research intervention scientists explore ways regulate pathways disease management. Despite numerous reviews detailing relationship between mechanisms, few delve into recent advancements nanomaterials mechanism for modulating pathway mitigate effects. Therefore, there urgent need fill this gap elucidate path use promising technology field treatment. This review article delves developments management through modulation, details mechanisms which drugs interact with pathways, highlights promise that nanomaterial holds driving forward

Language: Английский

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An assessment system for clinical and biological interpretability in ulcerative colitis

Aging, Journal Year: 2024, Volume and Issue: 16(4), P. 3856 - 3879

Published: Feb. 16, 2024

Aging | doi:10.18632/aging.205564. Shiqian Zhang, Ge Wenxiu Wang, Song-Bin Guo, Pengpeng Fuqi Quanbo Zhou, Zhaokai Yujia Haifeng Sun, Wenming Cui, Shuaixi Yang, Weitang Yuan

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Deciphering the prognostic features of bladder cancer through gemcitabine resistance and immune-related gene analysis and identifying potential small molecular drug PIK-75

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 3, 2024

Bladder cancer (BCa) stands out as a prevalent and highly lethal malignancy worldwide. Chemoresistance significantly contributes to recurrence progression. Traditional Tumor Node Metastasis (TNM) stage molecular subtypes often fail promptly identify treatment preferences based on sensitivity.

Language: Английский

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Model for predicting immunotherapy based on M2 macrophage infiltration in TNBC

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 14, 2023

Compared to other types of breast cancer, triple-negative cancer (TNBC) does not effectively respond hormone therapy and HER2 targeted therapy, showing a poor prognosis. There are currently limited number immunotherapeutic drugs available for TNBC, field that requires additional development.Co-expressing genes with M2 macrophages were analyzed based on the infiltration in TNBC sequencing data The Cancer Genome Atlas (TCGA) database. Consequently, influence these prognoses patients was analyzed. GO analysis KEGG performed exploring potential signal pathways. Lasso regression conducted model construction. scored by model, divided into high- low-risk groups. Subsequently, accuracy further verified using GEO database information from Center Sun Yat-sen University. On this basis, we prognosis prediction, correlation immune checkpoint, immunotherapy drug sensitivity different groups.Our findings revealed OLFML2B, MS4A7, SPARC, POSTN, THY1, CD300C significantly influenced TNBC. Moreover, finally determined construction, showed good prediction. And 50 therapeutic significance groups screened, which assessed possible immunotherapeutics have application demonstrated high precision our prognostic predictive analysis.MS4A7, CD300C, three main used offer clinical potential. Fifty medications their ability predict drugs, providing novel approach more reliable foundation applying subsequent treatments.

Language: Английский

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Cell death in tumor microenvironment: an insight for exploiting novel therapeutic approaches

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 10, 2025

Abstract Cell death is critical in tumor biology. The common cancer therapies can cause cell and alleviate tumor, while the cells develop a resistance to survive from therapies. Thus, not only observing alternative mechanisms of resistant death, but also understanding intricate dynamics processes within microenvironment (TME), are essential for tailoring effective therapeutic strategies. High-throughput sequencing technologies have revolutionized research by enabling comprehensive molecular profiling. Recent advances single unraveled heterogeneity TME components, shedding light on their complex interactions. In this review, we explored interplay between signaling TME, summarised potential drugs inducing pre-clinical stage, reviewed some studies applying next-generation research, discussed future utilization updated platforms screening novel treatment methods targeted death. conclusion, leveraging multi-omics dissect context holds great promise advancing therapy development.

Language: Английский

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Identification and validation of a pyroptosis-related prognostic model for colorectal cancer based on bulk and single-cell RNA sequencing data

World Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 15(2), P. 329 - 355

Published: Feb. 19, 2024

BACKGROUND Pyroptosis impacts the development of malignant tumors, yet its role in colorectal cancer (CRC) prognosis remains uncertain. AIM To assess prognostic significance pyroptosis-related genes and their association with CRC immune infiltration. METHODS Gene expression data were obtained from The Cancer Genome Atlas (TCGA) single-cell RNA sequencing dataset GSE178341 Expression Omnibus (GEO). Pyroptosis-related gene cell clusters was analyzed, enrichment analysis conducted. A risk model developed using LASSO regression algorithm, prediction accuracy assessed through K-M receiver operating characteristic analyses. nomogram predicting survival created, correlation between infiltration analyzed CIBERSORTx calculations. Finally, differential 8 normal samples verified by analyzing TCGA-COADREAD UCSC database. RESULTS An effective constructed genes-CHMP2B , SDHB BST2 UBE2D2 GJA1 AIM2 PDCD6IP SEZ6L2 (P < 0.05). Seven these exhibited based on TCGA database Patients higher scores demonstrated increased death reduced overall Significant differences observed low- high-risk groups, correlating expression. CONCLUSION We a for CRC, affirming This may prove useful evaluation.

Language: Английский

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Programmed Cell Death-Related Gene Signature Associated with Prognosis and Immune Infiltration and the Roles of HMOX1 in the Proliferation and Apoptosis were Investigated in Uveal Melanoma

Genes & Genomics, Journal Year: 2024, Volume and Issue: 46(7), P. 785 - 801

Published: May 20, 2024

Abstract Background Uveal melanoma (UVM) is the most common primary ocular malignancy, with a wide range of symptoms and outcomes. The programmed cell death (PCD) plays an important role in tumor development, diagnosis, prognosis. There still no research on relationship between PCD-related genes UVM. A novel PCD-associated prognostic model urgently needed to improve treatment strategies. Objective We aim screen signature investigate its proliferation ability apoptosis UVM cells. Methods clinical information RNA-seq data patients were collected from TCGA cohort. All classified using consensus clustering by selected genes. After univariate Cox regression PPI network analysis, then submitted LASSO analysis build model. level immune infiltration 8-PCD high- low-risk was analyzed xCell. prediction chemotherapy immunotherapy response assessed GDSC TIDE algorithm. CCK-8, western blot Annexin V-FITC/PI staining used explore roles HMOX1 Results total constructed risk score PCD negatively correlated overall survival, indicating strong predictive independent value. positively CD8 Tcm, Tem Th2 Immune cells high-risk group had poorer survival. drug sensitivity demonstrated that cisplatin might impact progression better responsiveness group. Finally, Overespression (OE-HMOX1) decreased viability induced Recuse experiment results showed ferrostatin-1 (fer-1) protected MP65 necrosis caused OE-HMOX1. Conclusion may have significant microenvironment, clinicopathological characteristics, prognosis sensitivity. More importantly, depletion greatly growth inhibited fer-1 This work provides foundation for effective therapeutic strategy tumour treatment.

Language: Английский

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Role of N6‐methyladenosine RNA modification in cancer

MedComm, Journal Year: 2024, Volume and Issue: 5(9)

Published: Sept. 1, 2024

Abstract N6‐methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells. Previous studies have shown that m6A pivotal diverse diseases especially cancer. corelates with initiation, progression, resistance, invasion, and metastasis However, despite these insights, a comprehensive understanding its specific roles mechanisms within complex landscape cancer still elusive. This review begins by outlining key regulatory proteins their posttranslational modifications (PTMs), as well role chromatin accessibility transcriptional activity Additionally, it highlights impact progression modulating programmed cell death affecting tumor microenvironment through various cancer‐associated immune Furthermore, discusses how microorganisms can induce enduring epigenetic changes oncogenic effect microorganism‐associated cancers altering modifications. Last, delves into immunotherapy, encompassing therapy, checkpoint blockade, cytokine adoptive transfer direct targeting regulators. Overall, this clarifies multifaceted explores targeted therapies aimed at manipulating modification, aiming to advance research improve patient outcomes.

Language: Английский

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