Journal Article Review Epublish
PubMed: 40166646 DOI: 10.1002/mco2.70152
STAT3 Signaling Pathway in Health and Disease.
MedComm (2020) 6(4):e70152
Authors: Md Abdus Samad, Iftikhar Ahmad, Aakifah Hasan, Mohammad Hassan Alhashmi, Arusha Ayub, Fahad A Al-Abbasi, Ajoy Kumer, Shams Tabrez
Affiliations
- Department of Biochemistry Faculty of Science King Abdulaziz University Jeddah Saudi Arabia.
- King Fahd Medical Research Center King Abdulaziz University Jeddah Saudi Arabia.
- Department of Biochemistry Faculty of Life Science Aligarh Muslim University Aligarh India.
- Department of Medical Laboratory Sciences Faculty of Applied Medical Sciences King Abdulaziz University Jeddah Saudi Arabia.
- Department of Medicine College of Health Sciences University of Georgia Georgia USA.
- Department of Chemistry College of Arts and Sciences International University of Business Agriculture & Technology (IUBAT) Dhaka Bangladesh.
Abstract
Signal transducer and activator of transcription 3 (STAT3) is a critical transcription factor involved in multiple physiological and pathological processes. While STAT3 plays an essential role in homeostasis, its persistent activation has been implicated in the pathogenesis of various diseases, particularly cancer, bone-related diseases, autoimmune disorders, inflammatory diseases, cardiovascular diseases, and neurodegenerative conditions. The interleukin-6/Janus kinase (JAK)/STAT3 signaling axis is central to STAT3 activation, influencing tumor microenvironment remodeling, angiogenesis, immune evasion, and therapy resistance. Despite extensive research, the precise mechanisms underlying dysregulated STAT3 signaling in disease progression remain incompletely understood, and no United States Food and Drug Administration (USFDA)-approved direct STAT3 inhibitors currently exist. This review provides a comprehensive evaluation of STAT3's role in health and disease, emphasizing its involvement in cancer stem cell maintenance, metastasis, inflammation, and drug resistance. We systematically discuss therapeutic strategies, including JAK inhibitors (tofacitinib, ruxolitinib), Src Homology 2 domain inhibitors (S3I-201, STATTIC), antisense oligonucleotides (AZD9150), and nanomedicine-based drug delivery systems, which enhance specificity and bioavailability while reducing toxicity. By integrating molecular mechanisms, disease pathology, and emerging therapeutic interventions, this review fills a critical knowledge gap in STAT3-targeted therapy. Our insights into STAT3 signaling crosstalk, epigenetic regulation, and resistance mechanisms offer a foundation for developing next-generation STAT3 inhibitors with greater clinical efficacy and translational potential.
MeSH
Microscopy, Electron, Scanning Transmission, Pharmaceutical Preparations, Cardiovascular Diseases, Neoplasms, United States Food And Drug Administration, Therapeutics
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