Although the JAK2/STAT3 pathway has been implicated in various cancers, the systematic evaluation of fedratinib (a selective JAK2 inhibitor) in ESCC, particularly using a combination of cell lines, xenograft models, and patient-derived organoids (PDOs) to validate its efficacy and mechanism, has not been previously reported. The gene discussed is JAK2; the disease is esophageal squamous cell carcinoma.