Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy DOI Creative Commons
Yujeong Moon, Seong Ik Jeon, Man Kyu Shim

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(2), P. 411 - 411

Published: Jan. 26, 2023

Proteolysis-targeting chimeras (PROTACs) are rapidly emerging as a potential therapeutic strategy for cancer therapy by inducing the degradation of tumor-overexpressing oncogenic proteins. They can specifically catalyze target proteins recruiting E3 ligases and utilizing ubiquitin-proteasome pathway. Since their mode action is universal, irreversible, recyclable, long-lasting, applicable to ‘undruggable’ proteins, PROTACs gradually replacing role conventional small molecular inhibitors. Moreover, application areas being expanded immunotherapy various types that involved in immunosuppressive tumor microenvironments. However, poor water solubility low cell permeability considerably restrict pharmacokinetic (PK) property, which necessitates use appropriate delivery systems immunotherapy. In this review, general characteristics, developmental status, PK first briefly covered. Next, recent studies on passive or active targeting introduced, effects tumor-targeting ability described. Finally, drug summarized. The adoption an adequate system PROTAC expected accelerate clinical translation PROTACs, well improve its efficacy therapy.

Language: Английский

RNA modifications: importance in immune cell biology and related diseases DOI Creative Commons
Lian Cui, Rui Ma,

Jiangluyi Cai

et al.

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

Published: Sept. 22, 2022

RNA modifications have become hot topics recently. By influencing processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune abnormality in human diseases is also a research focus progressing rapidly these years. Studies demonstrated that participate the multiple biological processes cells, development, differentiation, activation, migration, polarization, thereby modulating responses are involved some related diseases. In this review, we present existing knowledge functions underlying mechanisms modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, summarize their roles Via regulating can pathogenesis diseases, such cancers, infection, inflammatory autoimmune We further highlight challenges future directions based on knowledge. All all, review will provide helpful well novel ideas for researchers area.

Language: Английский

Citations

197
The roles and implications of RNA m6A modification in cancer DOI
Xiaolan Deng, Ying Qing, David Horne

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(8), P. 507 - 526

Published: May 23, 2023

Language: Английский

Citations

176
YTHDF2 orchestrates tumor-associated macrophage reprogramming and controls antitumor immunity through CD8+ T cells DOI
Shoubao Ma, Baofa Sun, Songqi Duan

et al.

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(2), P. 255 - 266

Published: Jan. 19, 2023

Language: Английский

Citations

119
Acetyltransferase NAT10 regulates the Wnt/β-catenin signaling pathway to promote colorectal cancer progression via ac4C acetylation of KIF23 mRNA DOI Creative Commons

Chi Jin,

Tuo Wang, Dongsheng Zhang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Dec. 15, 2022

N

Language: Английский

Citations

83
The Notch signaling pathway: a potential target for cancer immunotherapy DOI Creative Commons
Xinxin Li, Xianchun Yan, Yufeng Wang

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: May 2, 2023

Dysregulation of the Notch signaling pathway, which is highly conserved across species, can drive aberrant epigenetic modification, transcription, and translation. Defective gene regulation caused by dysregulated often affects networks controlling oncogenesis tumor progression. Meanwhile, modulate immune cells involved in anti- or pro-tumor responses immunogenicity. A comprehensive understanding these processes help with designing new drugs that target signaling, thereby enhancing effects cancer immunotherapy. Here, we provide an up-to-date overview how intrinsically regulates alterations stromal extrinsically regulate microenvironment (TME). We also discuss potential role immunity mediated gut microbiota. Finally, propose strategies for targeting These include oncolytic virotherapy combined inhibition nanoparticles (NPs) loaded regulators to specifically tumor-associated macrophages (TAMs) repolarize their functions remodel TME, combining specific efficient inhibitors activators checkpoint blockers (ICBs) synergistic anti-tumor therapy, implementing a customized effective synNotch circuit system enhance safety chimeric antigen receptor (CAR) cells. Collectively, this review aims summarize shapes improve

Language: Английский

Citations

83
Epigenetic modification of m6A regulator proteins in cancer DOI Creative Commons
Yumin Wang, Yan Wang, Harsh Patel

et al.

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

Published: June 30, 2023

Divergent N6-methyladenosine (m6A) modifications are dynamic and reversible posttranscriptional RNA that mediated by m6A regulators or methylation regulators, i.e., methyltransferases ("writers"), demethylases ("erasers"), m6A-binding proteins ("readers"). Aberrant associated with cancer occurrence, development, progression, prognosis. Numerous studies have established aberrant function as either tumor suppressors oncogenes in multiple types. However, the functions mechanisms of remain largely elusive should be explored. Emerging suggest can modulated epigenetic modifications, namely, ubiquitination, SUMOylation, acetylation, methylation, phosphorylation, O-GlcNAcylation, ISGylation, lactylation via noncoding action, cancer. This review summarizes current roles The for modification genesis segregated. will improve understanding regulatory regulators.

Language: Английский

Citations

83
m6A methylation: a process reshaping the tumour immune microenvironment and regulating immune evasion DOI Creative Commons
Xiaoxue Cao,

Qishun Geng,

Danping Fan

et al.

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

Published: March 1, 2023

Abstract N6-methyladenosine (m 6 A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m A writers, erasers, and readers, modulation involved myriad physiological pathological processes. Extensive studies have demonstrated diverse tumours, with effects on tumorigenesis, metastasis, resistance. Recent evidence has revealed an emerging role of tumour immunoregulation, divergent patterns been microenvironment. To depict regulatory immune microenvironment (TIME) its effect evasion, this review focuses TIME, which characterized hypoxia, metabolic reprogramming, acidity, immunosuppression, outlines A-regulated TIME evasion under stimuli. Furthermore, anti-tumour cells are summarized.

Language: Английский

Citations

56
Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells DOI Creative Commons
Cheng Cheng,

Peiwen Wang,

Yi Yang

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(22)

Published: May 28, 2023

Abstract Lung cancer is a commonly diagnosed disease worldwide, with non‐small cell lung cancers (NSCLCs) accounting for ≈ 85% of cases. Cigarette smoke an environmental exposure promoting progression NSCLC, but its role poorly understood. This study reports that smoking‐induced accumulation M2‐type tumor‐associated macrophages (M2‐TAMs) surrounding NSCLC tissues promotes malignancy. Specifically, extracellular vesicles (EVs) from cigarette extract (CSE)‐induced M2 promoted malignancy cells in vitro and vivo. circEML4 EVs CSE‐induced transported to cells, where it reduced the distribution ALKBH5 nucleus by interacting Human AlkB homolog H5 (ALKBH5), resulting elevated N6‐methyladenosine (m6A) modifications. m6A‐seq RNA‐seq revealed suppressor cytokine signaling 2 (SOCS2)‐mediated activation Janus kinase‐signal transducer activator transcription (JAK‐STAT) pathway regulating m6A modification SOCS2 via ALKBH5. Down‐regulation reversed EVs‐enhanced tumorigenicity metastasis cells. Furthermore, this found smoking patients showed increase circEML4‐positive M2‐TAMs. These results indicate M2‐TAMs promote through ALKBH5‐regulated SOCS2. also reveals TAMs acts as diagnostic biomarker especially history.

Language: Английский

Citations

42
The role of RNA methylation in tumor immunity and its potential in immunotherapy DOI Creative Commons
Yan Li,

Haoer Jin,

Qingling Li

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

Citations

30
YTHDF2 Is a Therapeutic Target for HCC by Suppressing Immune Evasion and Angiogenesis Through ETV5/PD‐L1/VEGFA Axis DOI Creative Commons
Jingyuan Wen, Xue Lin, Wei Yi

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 21, 2024

Abstract N6‐methyladenosine (m 6 A) modification orchestrates cancer formation and progression by affecting the tumor microenvironment (TME). For hepatocellular carcinoma (HCC), immune evasion angiogenesis are characteristic features of its TME. The role YTH RNA binding protein 2 (YTHDF2), as an m A reader, in regulating HCC TME not fully understood. Herein, it is discovered that trimethylated histone H3 lysine 4 27 acetylation promoter region YTHDF2 enhanced expression HCC, upregulated predicted a worse prognosis. Animal experiments demonstrated Ythdf2 depletion inhibited spontaneous formation, while overexpression promoted xenografted progression. Mechanistically, recognized 5′‐untranslational ETS variant transcription factor 5 (ETV5) mRNA recruited eukaryotic translation initiation 3 subunit B to facilitate translation. Elevated ETV5 induced programmed death ligand‐1 vascular endothelial growth A, thereby promoting angiogenesis. Targeting via small interference RNA‐containing aptamer/liposomes successfully both Together, this findings reveal potential application prognosis targeted treatment.

Language: Английский

Citations

26