{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSignal transducer and activator of transcription 3 (STAT3) is a pivotal transcription factor that integrates signals from cytokines and growth factors to regulate gene expression, thereby impacting both normal physiology and disease. In the context of cancer, persistently activated STAT3 orchestrates multiple pro‐tumorigenic processes by up‐regulating genes that drive cell proliferation, survival, invasion, angiogenesis, and epithelial–mesenchymal transition. STAT3 acts as a key mediator in the tumor microenvironment by cross‐talking with pathways such as NF‑κB and IL‑6/JAK signaling, and by even influencing metabolic reprogramming via its mitochondrial functions to sustain Ras‐driven malignant transformation. In parallel, mutations or dysregulation of STAT3 underlie important immune disorders—for instance, dominant‐negative mutations in STAT3 cause hyper‑IgE syndrome and impair differentiation of T helper 17 cells, while genome‐wide association studies have linked STAT3 to inflammatory diseases such as Crohn’s disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent advances have underscored STAT3 as a highly promising therapeutic target. Inhibition of STAT3—whether by small molecules, dominant‐negative mutants, antisense oligonucleotides, or innovative strategies such as the incorporation of cytokine‐signaling domains into chimeric antigen receptors (CARs)—has been shown to attenuate tumor growth, disrupt chemoresistance, and reprogram the immunosuppressive tumor milieu. Such approaches not only directly blunt STAT3‑mediated transcription of oncogenic and angiogenic factors (for example, genes encoding VEGF and survivin) but can also help restore effective anti‑tumor immunity by reducing the expression of factors like PD‑L1 and by modulating the activity of tumor‐associated immune cells. As ongoing research continues to unravel the complex network of STAT3 signaling in the interplay between inflammation, oncogenesis, and immune evasion, these insight are paving the way for rational combination therapies and precision treatments for both cancer and autoimmune disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "47"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Guilian Niu, Kenneth L Wright, Mei Huang, et al. 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