chidamide + decitabine

Chidamide + decitabine is a combination therapy of two small molecule drugs with epigenetic mechanisms, investigated primarily for hematological malignancies such as acute myeloid leukemia (AML) and Hodgkin lymphoma. Chidamide is an oral, selective histone deacetylase inhibitor (HDACi) targeting HDAC1, HDAC2, HDAC3, and HDAC10. It induces tumor cell apoptosis and cell cycle arrest by increasing acetylation of histones and reactivating silenced tumor suppressor genes. Decitabine is a DNA methyltransferase inhibitor (a hypomethylating agent), which demethylates DNA to reactivate silenced genes involved in differentiation and apoptosis. The combination has shown synergistic anti-leukemic effects in preclinical studies by enhancing apoptosis through upregulation of pro-apoptotic proteins (such as Bax, Caspase-3/9), downregulation of anti-apoptotic proteins (Bcl-2/BCL-XL), induction of p21 expression, increased acetylated histone H3/H3K9 levels, upregulation of the PERP gene—a TP53 target—and reactivation of other tumor suppressor genes like PU.1 and KLF4[1][2][4][6][8]. This dual epigenetic modulation offers a promising strategy for treating refractory or relapsed AML and Hodgkin lymphoma.