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The combination of chidamide, azacitidine, and thalidomide (often referred to as the CAT regimen) is an investigational therapy primarily being evaluated for the treatment of relapsed or refractory angioimmunoblastic T-cell lymphoma (AITL). This regimen leverages the synergistic potential of epigenetic modulation and immunomodulation. **Chidamide** (tucidinostat) is a selective histone deacetylase (HDAC) inhibitor targeting HDAC1, 2, 3, and 10, which promotes epigenetic reprogramming and induces cell cycle arrest. **Azacitidine** is a hypomethylating agent that inhibits DNA methyltransferases (DNMTs), leading to the reactivation of silenced tumor suppressor genes. **Thalidomide** is an immunomodulatory drug (IMiD) that binds to cereblon (CRBN), part of an E3 ubiquitin ligase complex, resulting in the degradation of transcription factors like Ikaros and Aiolos and altering the tumor microenvironment. This triple combination is particularly relevant for AITL, a disease characterized by a high frequency of mutations in epigenetic regulators such as TET2, DNMT3A, and IDH2.
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