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

Nanocarrier-mediated modulation of cGAS-STING signaling pathway to disrupt tumor microenvironment DOI
Sai Kiran S. S. Pindiprolu,

Madhu Tanya Singh,

Magham Sai Varshini

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Language: Английский

Citations

0
Phase I dose-escalation and pharmacodynamic study of STING agonist E7766 in advanced solid tumors DOI Creative Commons
Jason J. Luke, David J. Pinato, Dejan Juric

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(2), P. e010511 - e010511

Published: Feb. 1, 2025

E7766 is a novel stimulator of interferon genes (STING) agonist, capable potent activation immune cells and generating strong antitumor response in preclinical murine tumor models. Here we present the safety, efficacy, biomarker results first-in-human phase I/Ib study intratumoral patients with advanced solid tumors. Eligible relapsing/refractory cancers (n=24) were enrolled dose-escalating cohorts to receive injections from 75 1000 µg. The most frequent treatment-related treatment-emergent adverse events chills (50.0%; 85.7%), fever (40.0%; fatigue (30.0%; 35.7%) who received non-visceral visceral injections, respectively. Eight (33.3%) achieved stable disease as their best per modified Response Evaluation Criteria In Solid Tumors version 1.1 variability between injected non-injected lesions. Plasma levels IFN-α, IFN-β, IFN-γ, TNF-α, IL-6, IP-10, MCP1, MIP1b transiently increased all evaluable within 10 hours postinjection, then dropped baseline levels. Levels blood gene expression interferon-related STING tested. Further increases programmed death ligand 1 cluster differentiation 8 at both RNA protein also observed some across dose total, generated on-target pharmacodynamic effects exploration homogeneous patient population necessary assess efficacy.

Language: Английский

Citations

0
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

0