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Azacitidine + glasdegib is an investigational combination therapy consisting of azacitidine, a pyrimidine nucleoside analogue with DNA hypomethylating and cytotoxic activity, and glasdegib, an oral small molecule inhibitor of the Hedgehog signaling pathway through inhibition of Smoothened. This combination is being studied for the treatment of adult patients with previously untreated acute myeloid leukemia (AML), particularly in those who are not candidates for intensive induction chemotherapy. Azacitidine inhibits DNA methyltransferase, leading to impaired DNA methylation and disruption of RNA and DNA synthesis. Glasdegib targets the Hedgehog pathway, which plays a role in leukemic stem cell maintenance and the pathogenesis of AML, aiming to suppress leukemic stem cells and prevent relapse[1][2][3][4][5][6].
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