volasertib + azacitidine

**Volasertib + azacitidine** is an experimental combination of two small-molecule drugs used in the treatment of hematologic malignancies, specifically myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). - **Volasertib** is a selective small-molecule inhibitor of Polo-like kinase 1 (PLK1), a serine/threonine kinase essential for cell cycle progression through mitosis. Inhibition of PLK1 leads to mitotic arrest and apoptosis in proliferating cancer cells. - **Azacitidine** is a hypomethylating agent and nucleoside metabolic inhibitor that incorporates into DNA and RNA, inhibiting DNA methyltransferase, causing DNA hypomethylation and cell differentiation or apoptosis in malignant cells. This combination has been studied due to potential synergistic anti-leukemic effects in preclinical and early-phase clinical studies, typically administered intravenously (volasertib) and subcutaneously (azacitidine). Clinical development was mainly led by Boehringer Ingelheim, but further development was terminated for non-clinical reasons. Observed toxicities include substantial hematological adverse effects such as thrombocytopenia and neutropenia. The combination aims to exploit non-overlapping mechanisms for potentially improved efficacy in disease settings resistant or refractory to hypomethylating agents alone[4][1][2][5].