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5-azacytidine + doxorubicin is a combination of two chemotherapeutic agents used experimentally and in some clinical settings for the treatment of various cancers. - **5-azacytidine** is a nucleoside analog that acts as a DNA methyltransferase inhibitor, leading to hypomethylation of DNA and reactivation of silenced tumor suppressor genes. This epigenetic modulation can sensitize cancer cells to other chemotherapeutic agents. - **Doxorubicin** is an anthracycline antibiotic that intercalates into DNA, inhibits topoisomerase II, and generates free radicals, resulting in DNA damage and apoptosis. The combination has been studied for its potential synergistic effects in preclinical models (e.g., leukemia L1210 cells) and case reports (e.g., mesothelioma), with evidence suggesting that sequential administration may enhance cytotoxicity compared to simultaneous dosing. Preclinical studies also show enhanced chemosensitivity when cancer cells are pretreated with 5-azacytidine before exposure to doxorubicin[1][2][3][6].
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