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

Essays in Biochemistry, Год журнала: 2025, Номер 69(02)

Опубликована: Март 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.

Язык: Английский

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Alginate sulfated polysaccharide TGC161 exhibits antitumor activity via suppression of STING activation-mediated T-cell apoptosis

Carbohydrate Polymer Technologies and Applications, Год журнала: 2025, Номер unknown, С. 100759 - 100759

Опубликована: Март 1, 2025

Язык: Английский

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Organelle-oriented nanomedicines in tumor therapy: Targeting, escaping, or collaborating?

Bioactive Materials, Год журнала: 2025, Номер 49, С. 291 - 339

Опубликована: Март 13, 2025

Язык: Английский

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Engineered NK Exosomes Captured Antigens In Situ for Enhanced Tumor Immunotherapy

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Natural killer (NK) cells are widely involved in the field of tumor immunotherapy due to their unique killing ability. However, durability and efficacy NK-cell monotherapy facing great challenges owing limitation immunosuppressive microenvironment (TME). NK cell-derived exosomes (Neo) not only play an innate immunomodulatory role similar but also emerge as promising antitumor nanocarriers. In this study, engineered Neo (R@Neo-MN) was designed that encapsulates multifunctional drug (Raddeanin a, RA) modified with maleimide (Mal, M) mannose (Man, N). The obtained R@Neo-MN could exert cell-like function induce immunogenic cell death tumors release tumor-associated antigens (TAAs). Furthermore, activated cyclic guanosine monophosphate-adenosine monophosphate synthase/interferon gene stimulator (cGAS/STING) type I interferons (IFN). Then, capture TAAs through Mal specifically target dendritic (DCs) Man, thereby promoting maturation DCs enhancing tumor-specific cytotoxic T-cell (CTL)-mediated adaptive immunity. released IFN further promoted infiltration activition CTLs at site. Our study suggested a novel strategy harnesses both immunity for enhanced immunotherapy.

Язык: Английский

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STING Inhibitors and Degraders: Potential Therapeutic Agents in Inflammatory Diseases

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 291, С. 117632 - 117632

Опубликована: Апрель 15, 2025

Язык: Английский

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