Cyclic GMP-AMP Synthase in Cancer Prevention DOI Open Access
Weidong Chen, Ga-Eun Lee, Dohyun Jeung

et al.

Journal of Cancer Prevention, Journal Year: 2023, Volume and Issue: 28(4), P. 143 - 149

Published: Dec. 30, 2023

Cyclic GMP-AMP (cGAMP), synthesized by cGAMP synthase (cGAS), serves as a secondary messenger that modulates various cellular processes, including cell proliferation, death, immune response, and inflammation.cGAS is activated upon detecting cytoplasmic DNA, which may originate from damaged genomic mitochondrial DNA or viral bacterial infections.The presence of in the cytoplasm can trigger substantial inflammatory reaction cytokine production via cGAS-STING signaling pathway.Consequently, specific inhibitors targeting this pathway hold significant potential chemopreventive agents.In review, we explore effectiveness modulating cGAS activity.We discuss role cGAMP, mechanism action for distinguishing between self foreign possible functions within nucleus.

Language: Английский

Radiotherapy and immunology DOI Creative Commons
Liangliang Wang, Connor Lynch, Sean P. Pitroda

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(7)

Published: May 21, 2024

The majority of cancer patients receive radiotherapy during the course treatment, delivered with curative intent for local tumor control or as part a multimodality regimen aimed at eliminating distant metastasis. A major focus research has been DNA damage; however, in past two decades, emphasis shifted to important role immune system plays radiotherapy-induced anti-tumor effects. Radiotherapy reprograms microenvironment, triggering and RNA sensing cascades that activate innate immunity ultimately enhance adaptive immunity. In opposition, also induces suppression immunity, including recruitment regulatory T cells, myeloid-derived suppressor suppressive macrophages. balance pro- is regulated by chemokines cytokines. Microbiota can influence outcomes under clinical investigation. Blockade PD-1/PD-L1 axis CTLA-4 extensively investigated combination radiotherapy; we include review trials involving inhibition these checkpoints radiotherapy.

Language: Английский

Citations

30

New insight in immunotherapy and combine therapy in colorectal cancer DOI Creative Commons
Kai Ji,

Hang Jia,

Zixuan Liu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 7, 2025

The advent of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) treatment marks a major breakthrough. These therapies have proven safer and more effective than traditional radiotherapy targeted treatments. Immunotherapies like pembrolizumab, nivolumab, ipilimumab pioneered new avenues, potentially improving patient outcomes quality life. Additionally, advances immunotherapy prompted detailed research into CRC therapies, especially those integrating ICIs with conventional treatments, providing hope for patients shaping future practice. This review delves the mechanisms various evaluates their therapeutic potential when combined radiotherapy, chemotherapy, clinical settings. It also sheds light on current application involving treatment.

Language: Английский

Citations

2

cGLRs Join Their Cousins of Pattern Recognition Receptor Family to Regulate Immune Homeostasis DOI Open Access
Vijay Kumar, John H. Stewart

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1828 - 1828

Published: Feb. 2, 2024

Pattern recognition receptors (PRRs) recognize danger signals such as PAMPs/MAMPs and DAMPs to initiate a protective immune response. TLRs, NLRs, CLRs, RLRs are well-characterized PRRs of the host system. cGLRs have been recently identified PRRs. In humans, cGAS/STING signaling pathway is part cGLRs. cGAS recognizes cytosolic dsDNA PAMP or DAMP STING-dependent response comprising type 1 IFN release, NF-κB activation, autophagy, cellular senescence. The present article discusses emergence critical how they regulate responses. We examined role signaling, well-studied cGLR system, in activation following sections discuss dysregulation disease cross-talk with other maintains homeostasis. This understanding will lead design better vaccines immunotherapeutics for various diseases, including infections, autoimmunity, cancers.

Language: Английский

Citations

9

Pattern-Recognition Receptors and Immunometabolic Reprogramming: What We Know and What to Explore DOI Creative Commons
Vijay Kumar, John H. Stewart

Journal of Innate Immunity, Journal Year: 2024, Volume and Issue: 16(1), P. 295 - 323

Published: Jan. 1, 2024

Evolutionarily, immune response is a complex mechanism that protects the host from internal and external threats. Pattern-recognition receptors (PRRs) recognize MAMPs, PAMPs, DAMPs to initiate protective pro-inflammatory response. PRRs are expressed on cell membranes by TLR1, 2, 4, 6 in cytosolic organelles TLR3, 7, 8, 9, NLRs, ALRs, cGLRs. We know their downstream signaling pathways controlling immunoregulatory However, impact of metabolic control cells pro- anti-inflammatory activity has not been discussed extensively.

Language: Английский

Citations

7

Role of Cell Adhesion in Cancer Metastasis Formation: A Review DOI Creative Commons

Denis Burčík,

Ján Macko, Natália Podrojková

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: 10(6), P. 5193 - 5213

Published: Feb. 9, 2025

Intercellular adhesion is accompanied by several physical quantities and actions. In this review, we tried to collect information about the influence of surface energy its impact on cell-cell adhesion. It still undergoes development for cancer treatment. Data receptor-ligand interactions that occur circulating tumor cells (CTCs) are described, receptors as therapeutic targets collected. Additionally, roughness between CTC was monitored. The effects different cell molecules (CAMs) adhesion, growth, proliferation were investigated. This review offers general principles through blockade with blocking drugs inhibitors like computational models describe process Some theoretical based minimum total free interaction CAMs selected organic have been presented. final aim find how modulation CTCs (by medicals or physically) inhibits metastases formation.

Language: Английский

Citations

1

The cGAS-STING pathway in cancer immunity: dual roles, therapeutic strategies, and clinical challenges DOI Creative Commons

Beilei Yue,

Wenbo Gao, Jonathan F. Lovell

et al.

Essays in Biochemistry, Journal Year: 2025, Volume and Issue: 69(02)

Published: March 7, 2025

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a crucial component the host's innate immunity and plays central role in detecting cytosolic double-stranded DNA from endogenous exogenous sources. Upon activation, cGAS synthesizes cGAMP, which binds to STING, triggering cascade immune responses, including production type I interferons pro-inflammatory cytokines. In context cancers, cGAS-STING can exert dual roles: on one hand, it promotes anti-tumor by enhancing antigen presentation, stimulating T-cell inducing direct tumor cell apoptosis. On other chronic particularly tumors with chromosomal instability, lead suppression progression. Persistent signaling results up-regulation checkpoint molecules such as PD-L1, contributing evasion metastasis. Consequently, strategies targeting have consider balance activation tolerance caused activation. This review explores mechanisms underlying both protumor roles pathway, focus potential therapeutic approaches, challenges faced their clinical application, along corresponding solutions.

Language: Английский

Citations

1

Harnessing the cGAS-STING pathway to potentiate radiation therapy: current approaches and future directions DOI Creative Commons

Nicholas Colangelo,

Naamit K. Gerber, Ralph E. Vatner

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 10, 2024

In this review, we cover the current understanding of how radiation therapy, which uses ionizing to kill cancer cells, mediates an anti-tumor immune response through cGAS-STING pathway, and STING agonists might potentiate this. We examine signaling release inflammatory cytokines in nuclear mitochondrial DNA entering cytoplasm. The significance context is explored, such as cell-damaging therapies genomic instability. contribution non-immune cells tumor microenvironment considered. This review also discusses burgeoning that independent cytokine various mechanisms by can evade signaling. available data on stimulates well may induced radiation. There discussion novel modalities affect conclude with a ongoing planned clinical trials combining therapy agonists, provide insights consider when planning future these treatments.

Language: Английский

Citations

6

Epigenetic modulation of immune cells: Mechanisms and implications DOI
Stefano Fiordoro, Camillo Rosano,

Eugenia Pechkova

et al.

Advances in Biological Regulation, Journal Year: 2024, Volume and Issue: 94, P. 101043 - 101043

Published: Aug. 10, 2024

Language: Английский

Citations

5

Make it STING: nanotechnological approaches for activating cGAS/STING as an immunomodulatory node in osteosarcoma DOI Creative Commons
John O’Donoghue, Fiona E. Freeman

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 30, 2024

Osteosarcoma is a highly aggressive bone cancer primarily affecting children, adolescents, and young adults. The current gold standard for treatment of osteosarcoma patients consists two to three rounds chemotherapy, followed by extensive surgical intervention from total limb reconstruction amputation, additional chemotherapy. Although chemotherapy has advanced the significantly, overall 5-year survival rate in resistant forms still below 20%. interaction between immune system long been recognized as critical aspect tumour growth. Tumour cells within microenvironment (TME) suppress antitumour immunity, immunosuppressive cytokines provide extrinsic factors drug resistance. Emerging research demonstrates an immunostimulatory role cGAS/STING pathway osteosarcoma, typically considered immune-cold or immunosuppressed type. signalling appears drive innate response against tumours potentiates efficacy other common therapies including chemo radiotherapy. Nanotechnological delivery systems improved therapy have also under investigation recent years. This review provides overview signalling, its divergent roles context cancer, collates which activates adjuvant immunomodulatory target osteosarcoma. It will discuss nanotechnological approaches that developed stimulate cGAS/STING. Finally, it highlight future directions we believe be central development this transformative field.

Language: Английский

Citations

3

Accelerating and protective effects toward cancer growth in cGAS and FcgRIIb deficient mice, respectively, an impact of macrophage polarization DOI
Arthid Thim-uam,

Papasara Chantawichitwong,

Pornpimol Phuengmaung

et al.

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: April 24, 2025

Language: Английский

Citations

0