Methods of malignant tumors therapy by targeting the STING pathway

A major challenge in modern oncology is the development of new antitumor agents that induce durable remission with minimal side effects. One promising strategy involves immunotherapy and the design of chemical compounds for targeted activation of innate immunity. The intracellular protein STING (stimulator of interferon genes) plays a key role in this process by mediating the production of type I interferons, which exhibit potent antiviral and antitumor activity. Systemic interferon treatment often causes side effects, driving the need for methods to locally stimulate interferon production within the tumor microenvironment via the STING pathway. The direct STING activator, cyclic dinucleotide cGAMP, synthesized by cGAS (cyclic GMP-AMP-synthase) from ATP and GTP is unstable and rapidly hydrolyzed, limiting its therapeutic application. Global research efforts are focused on developing novel, stable STING agonists. Incorporating STING activators into antibody-drug conjugates (ADCs) could enhance treatment efficacy. ADCs enable targeted delivery of the potent agonist directly to the tumor site via a monoclonal antibody specific to a tumor-associated antigen. Because tumor cells often develop resistance to standard chemotherapy, ADCs with STING-agonists could be a better treatment option. While several ADCs with STING-agonists have shown promise in preclinical studies, further detailed investigation of their properties and components is essential to optimize their efficacy and tolerability for clinical translation. The following databases were used: PubMed, elibrary, Google Scholar, NCBI ClinicalTrials, PubChem. Search period: June 2025 – August 2025. Key search terms: STING protein, cGAS protein, cGAS-STING pathway, IFN-β, Interferon-based treatment, Type I IFN induction, Antibody-drug conjugate, STING activation, STING agonist, HER2-targeted therapies.