STING (stimulator of interferon response cGAMP interactor 1)

Patients with liver metastases exhibited T cell senescence and metabolic hyperactivation, correlating with therapeutic resistance. These findings highlight that pre-existing tumor immunogenicity and T cell functional capacity are associated with response to RIN therapy, and that RIN treatment may facilitate both systemic T cell activation and local TME modulation.

Dysregulated Golgi-to-ER traffic underlies the pathogenesis of COPA syndrome, a monogenic autoinflammatory disease caused by missense mutations of coatomer protein complex subunit α (COP-α). In this chapter, I focus on emerging issues regarding the regulation of STING activation by membrane traffic between the ER and the Golgi, and also on the molecular mechanism underlying the specific activation of TBK1/IRF3 at the TGN.

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.

ENPP3 is a hypoxia-driven, cGAMP-targeting innate immune checkpoint in ccRCC. Its inhibition reactivates STING-dependent anti-tumor immunity, providing a strong preclinical rationale for targeting ENPP3 therapeutically.

We further discuss current challenges and future perspectives for this innovative combinatorial immunotherapy approach. Overall, this article highlights promising nanomedicine-based avenues that leverage the cGAS-STING-cuproptosis interplay for cancer therapy.

Clinically, the BCL-2 inhibitor venetoclax has revolutionized CLL and acute myeloid leukemia (AML) treatment, showing efficacy in TP53-mutant CLL and elderly AML patients when combined with CD20 antibodies or hypomethylating agents...This review highlights the clinical success of BCL-2 inhibitors, addresses resistance mechanisms, and explores future directions, including sublethal MOMP, inflammatory outcomes, and novel inhibitors. Celebrating the collaborative, interdisciplinary efforts that transformed fundamental discoveries into life-saving therapies, this account underscores both the triumphs and the "potholes" encountered on the path to understanding apoptosis, while identifying open questions for ongoing research.

The upregulated LGALS1 is then secreted via SUSD2 assistance, ultimately suppressing CD8+ T cell function and inducing apoptosis. Our findings define a stromal-immune axis in pancreatic cancer, linking miR-181b-5p from CAFs to the establishment of an immune-suppressive niche via the STING pathway in tumor cells, thereby revealing this cascade as a targetable mechanism to counteract immune evasion.

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.

Proper activation of the pathway significantly enhances antitumor immune responses, while excessive activation or dysfunction promotes tumor progression. This article offers an in-depth analysis of the molecular mechanism associated with the pathway, its biological function in cancer, and the research progress of targeted drugs, seeking to investigate and create more potent therapeutic medications while also thoroughly examining the pathway's unique function.

Notably, depleting ERRα markedly attenuates breast tumor cell growth in vitro and in vivo, and our in vitro evidence indicates this occurs in part through activating STING signaling. These findings establish that the ERRα-KDM5C serves as a critical checkpoint for STING enhancer activity, revealing a regulatory mechanism of STING enhancer activity in breast tumor progression.

In contrast, early-phase clinical trials of STING agonists, including ADU-S100, SYNB1891, IMSA101, and MK-1454, have shown acceptable safety and pathway engagement but generally modest and variable clinical responses, primarily reflected by low objective response rates and limited disease stabilization. We highlight emerging drug delivery platforms, such as nanocarriers, antibody-drug conjugates, and exosome-based systems, as key modulators of efficacy and safety, and emphasize the importance of biomarker-guided approaches for patient stratification and trial optimization. By integrating biological insight with translational feasibility, this review provides a framework for advancing STING-based combination immunotherapy toward more durable and personalized cancer treatment.

IRF3 expression appears linked to histological subtypes, supporting its role in tumor biology. These markers may provide valuable insights into tumor behavior and may guide treatment strategies in CCA patients.