Precision Targeting of Sting: Challenges, Innovations, and Clinical Outlook for Cancer Therapy

Authors

Jiaqi Shi
Yingying Zhang
Na Zhao
Ekihiro Seki
Li Ma
Gordana Kocic
Xiaobo Li
Janoš Terzić
Tongsen Zheng

Language

English

Publication Date

1-5-2026

Journal

Innovation

DOI

10.1016/j.xinn.2025.101074

PMID

41737316

PMCID

PMC12925938

PubMedCentral® Posted Date

8-6-2025

PubMedCentral® Full Text Version

Post-print

Abstract

The stimulator of interferon genes (STING) pathway plays a crucial role in immune responses and has emerged as a compelling target in cancer therapy. Despite promising preclinical studies, clinical trials of STING agonists have largely failed to deliver durable efficacy, with no agents progressing to phase III trials. This review examines the biological, pharmacological, and clinical barriers limiting STING pathway activation in cancer treatment. We discuss the inherent limitations of STING agonists as well as host-related resistance driven by tumor heterogeneity, immune suppression, and chronic STING activation. Mechanisms of acquired resistance, such as immune checkpoint upregulation and suppression of effector immune cells, are also reviewed. Recent advances in delivery platforms, small-molecule design, and combination treatment strategies offer promising paths forward. We highlight precision approaches based on human STING variants, epigenetic modulation, and biomarker-driven patient stratification to improve clinical outcomes. These insights underscore the need for refined, context-specific STING activation strategies to unlock the full therapeutic potential of this pathway in oncology.

Keywords

STING, cancer, immunotherapy, clinical translation, resistance

Published Open-Access

yes

Recommended Citation

Shi, Jiaqi; Zhang, Yingying; Zhao, Na; et al., "Precision Targeting of Sting: Challenges, Innovations, and Clinical Outlook for Cancer Therapy" (2026). Faculty, Staff and Student Publications. 6233.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6233