CGAS (Cyclic GMP-AMP Synthase)

Combination of ATP-Mn CNP with immune checkpoint inhibitors achieved 37.5% tumor eradication in MC38 murine models, and significantly prolonged mice survival. This study establishes an ATP-fueled coordination strategy that harnesses ATP as both an assembly ligand and an immune stimulator to enhance Mn-mediated STING activation.

Context-dependent, non-canonical signaling and intercellular cGAMP transport and clearance further define developmental vulnerabilities and pharmacodynamic anchors. Together, these advances position cGAS-STING as a double-edged axis in urogenital oncology-one that offers powerful opportunities for immune reactivation while demanding precision strategies to avert protumor adaptation.

The source of IL-1β was not senescent fibroblasts, but M1 macrophages that accumulate with inflammaging. Collectively, these results suggest that aging up-regulates LCN2 expression in oral-related epithelial cells mainly via IL-1β secreted from M1 macrophages, rather than through the induction of their senescence.

Consistently, inhibition of mtDNA-repair enhances cellular sensitivity to ferroptosis and therefore synergizes with ferroptosis inducer in suppressing tumorigenesis in mouse xenograft tumor models. This study provides a fundamental understanding of how mPTP engages in ferroptosis by releasing mitochondrial DNAs as crucial messengers to activate ferroptotic signaling.

It was also linked to reduced cisplatin/paclitaxel sensitivity (P < 0.05) and lower immunotherapy response (29.04% vs. 45.05%, P = 0.015). These findings suggest that JAML deficiency may suppress cyclic GMP-AMP synthase (cGAS)-STING pathway activation, potentially contributing to M1/M2 macrophage polarization imbalance and facilitating EC progression. Clinically, JAML expression shows promise as a potential biomarker for prognostic stratification and treatment response prediction (chemotherapy/immunotherapy), providing insights for developing precision immunochemotherapy strategies in EC.

We established a novel MIRGs signature that accurately predicts CRC clinical outcome. Integration of manganese-based agents with immune checkpoint inhibitors (ICIs) represents a potential therapeutic strategy for immunotherapy-resistant CRC.

uncover a novel SPOP-USP7-TREX1 axis that controls cytosolic DNA clearance after DNA damage, thereby gating tumor-cell-intrinsic cyclic GMP-AMP synthase (cGAS)-STING activation and response to radioimmunotherapy. Compellingly, targeting USP7 and TREX1 might sharpen patient selection and combination strategies.

PRMT1 promotes CC progression by enhancing tumor growth, angiogenesis, and immune evasion, partly by regulating the cGAS-STING pathway. Hence, it may serve as a potential therapeutic target.

This review consolidates current mechanistic insights, preclinical evidence, and emergent clinical data regarding the cGAS-STING pathway in gastrointestinal cancers, while emphasising biomarker-guided patient stratification and AI-powered predictive tools that could facilitate the precise application of STING-targeted therapies.

Activating the cGAS-STING pathway can enhance IFN-γ secretion of NK cells to improve their cytotoxicity against gastric cancer cells, suggesting a therapeutic strategy for gastric cancer using NK cells combined with STING agonists.

In this review, we summarize recent molecular and cellular findings explaining how cancer cells suppress cGAS-STING through epigenetic regulation, post-translational modifications (PTMs), and altered metabolic pathways. We also evaluate recent studies on cGAS-STING agonists aimed at restoring sensitivity to chemotherapy, immunotherapy, and targeted cancer therapies to inform new strategies to pharmacologically reactivate cGAS-STING signaling pathway to reverse existing therapeutic barriers.