Over the past two decades, the stimulator of interferon genes (STING) pathway has emerged as a critical aspect of the immune system and a promising therapeutic target against cancers. The potential for STING-mediated anti-tumor immunity has prompted extensive research in both academia and the pharmaceutical industry, especially with regard to its ability to enhance patient response rates towards immune checkpoint blockades (ICB). Despite these exciting developments, effective and safe STING therapies are beset by significant challenges related to drug delivery. While there are many clinical trials of STING-ICB combination therapies for solid cancer treatments ongoing, few have been US Food and Drug Administration (FDA) approved to this date. Novel chemical and biological delivery strategies as well as mechanistic investigations are needed to realize the full therapeutic potential of this promising signaling pathway.

This Research Topic aims to:
1. Deepen our current understanding of the translational challenges of STING-based therapies, potential side effects such as toxicity to CD8 T cells or autoimmunity, as well as the fundamental mechanisms of STING signaling in various types of cells.
2. Design safe and effective STING-based cancer immunotherapies that addresses the current clinical translational challenges.

In this Research Topic we invite submissions addressing, but not limited to, the following themes:
· Novel drug delivery strategies for targeted and enhanced STING activation
· The interplay between STING activation and immune cell functions
· The synthesis and characterization of novel STING agonists
· Side effects of STING activation in cancer, such as off-target effects and immunological toxicity
· Biomarkers of STING activity and response to therapy in preclinical and clinical settings
· Combination therapies involving STING agonists and immune checkpoint inhibitors
· Development of STING agonists for the treatment of different cancer types
· STING activation in the context of host-microbiome interactions and the tumour microenvironment
· The role of STING in innate immune sensing and anti-viral responses

Dr. Yanpu He and Dr. Celestine Hong hold patents related to the Research Topic. All other members of the Editorial Team declare no competing interests.

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Frontiers in Chemical Biology

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