IMMUNE ACTIVATION IN METASTATIC CANCERS: THE STING PATHWAY AND NANOPARTICLE-BASED THERAPEUTIC APPROACHES

Cancer immunotherapy represents a significant treatment approach aimed at enhancing patient survival by targeting the tumor microenvironment and immune system. In recent years, considerable interest has been shown in novel therapeutic strategies that activate the immune system, particularly in patients with metastatic cancer. The stimulator of interferon genes pathway has been identified as a critical target due to its ability to enhance immune responses against malignancies. The stimulator of interferon genes adaptor protein plays a central role in cellular immune signaling and is an essential component of the deoxyribonucleic acid sensing machinery. Upon activation, the stimulator of interferon genes pathway induces the production of various cytokines, mainly type I interferons, to trigger an immune response in the tumor microenvironment. However, direct administration of stimulator of interferon genes agonists poses significant challenges due to systemic toxicity and off-target effects. To overcome these limitations, nanoparticle-based drug delivery systems have been developed to enhance therapeutic efficacy and minimize side effects. These systems enhance stimulator of interferon genes activation, ensure targeted distribution, and amplify immune stimulation. This review discusses the role of the stimulator of interferon genes pathway in metastatic tumors, the mechanisms underlying nanoparticle-based stimulator of interferon genes agonists, and recent findings from preclinical studies and clinical trials. Additionally, it discusses the advantages, challenges, and potential directions for future research on this approach.