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This combination therapy consists of golidocitinib, azacitidine, and chidamide, and is being evaluated for the treatment of peripheral T-cell lymphoma (PTCL). Golidocitinib is a potent and highly selective Janus kinase 1 (JAK1) inhibitor that blocks the JAK/STAT signaling pathway, which is frequently dysregulated in T-cell malignancies. Azacitidine is a pyrimidine nucleoside analog that functions as a hypomethylating agent by inhibiting DNA methyltransferase, thereby reversing epigenetic silencing of tumor suppressor genes. Chidamide is a benzamide-based selective histone deacetylase (HDAC) inhibitor targeting HDAC1, 2, 3, and 10, which modulates the acetylation status of histones and non-histone proteins to induce cell cycle arrest and apoptosis. The rationale for this triplet regimen, investigated by Ruijin Hospital, is to leverage synergistic effects between JAK1 inhibition and epigenetic modulation (hypomethylation and HDAC inhibition) to overcome resistance and improve outcomes in PTCL patients, particularly those ineligible for intensive chemotherapy or transplantation.
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