Targeting the cGAS-STING Pathway in Gastrointestinal Cancers: Modulating Tumor-associated Inflammation for...

Gastrointestinal (GI) tumours are a significant contributor to cancer-related mortality, underscoring the necessity for novel therapeutic approaches. The cGAS-STING pathway, a cytosolic DNA-sensing mechanism, has two effects: it boosts antitumor immunity and also helps the tumour microenvironment inhibit the immune system.

This review integrates recent preclinical and clinical evidence regarding cGAS-STING signalling in gastrointestinal cancers, emphasising therapeutic strategies including STING agonists, immune checkpoint combinations, nanoparticle delivery, and pathway interactions with DNA damage response, autophagy, and immune surveillance.

Evidence indicates that cGAS-STING activation can improve immune surveillance and therapeutic efficacy; nevertheless, sustained activation may facilitate tumour growth via immune evasion and chronic inflammation. Preclinical evidence indicates the promise of STING agonists and combination treatments, whereas initial clinical trials yield optimistic, although constrained, results. Toxicity, tumour heterogeneity, and resistance mechanisms remain obstacles.

For therapy to work, it is important to find a balance between the two effects of cGAS- STING. Biomarker-guided medication development, rational combinations, and enhanced delivery technologies are some of the strategies that could lead to better outcomes. Predictive models powered by artificial intelligence also enable grouping patients and tailoring treatments to their needs.

One promising avenue for advancing precision oncology in gastrointestinal malignancies is targeting the cGAS-STING pathway. Enhancing efficacy and reshaping cancer treatment could be achieved by overcoming present limits through integrated therapeutic approaches and personalised medicine.