Blockade of the STAT3 pathway as a method of targeted antitumor therapy

Introduction . Cancer remains one of the most pressing medical and social problems, being a leading cause of disability and mortality worldwide. Contemporary antineoplastic pharmacotherapy is characterized by the development of novel therapeutic approaches, one of which has been the introduction of targeted therapy based on selective action on specific molecular targets critically important for the viability of tumor cells. Objective . To determine the role of the transcription factor STAT3 (Signal Transducer and Activator of Transcription 3) in tumor growth and to identify targeted therapeutic agents developed on the basis of its antagonists. Materials and methods . A narrative literature review was performed. PubMed/MEDLINE, eLIBRARY.RU and Google Scholar were searched for publications from 1997 to 2026 using the keywords “STAT3”, “JAK/STAT3”, “STAT3 inhibitor”, “STAT3 cancer” and their Russian equivalents. Original experimental and clinical studies, reviews, systematic reviews and meta-analyses published in English or Russian were included. Discussion . The principal groups of agents that block various steps of STAT3 activation include inhibitors of Janus kinases (JAK) (ruxolitinib, tofacitinib, fedratinib), inhibitors of the STAT3 SH2 domain (Stattic, S31-201, STA-21, BP-1-102), oligonucleotides (antisense and decoy oligonucleotides), and agents that prevent the binding of STAT3 to gene promoter regions. The main limitations of most of these agents include insufficient selectivity, pronounced toxicity, poor bioavailability, and the development of drug resistance. Novel delivery systems (including nanoparticles) and targeted protein degradation (PROTAC) are being developed to overcome them. A number of compounds are undergoing phase I–III clinical trials. Conclusion . The transcription factor STAT3 is one of the key regulators of tumor growth, angiogenesis, metastasis, and immune evasion. At the same time, STAT3 blockade represents a promising avenue in targeted antineoplastic therapy. Despite existing challenges, further study of the molecular biology of STAT3 and the improvement of targeted agents may lead to the development of selective and effective next-generation antineoplastic drugs.