Targeting polo-like kinase 1 in acute myeloid leukemia

Polo-like kinase 1 (Plk1) plays a number of important roles in the passage of cells through mitosis. It is expressed at high levels in a variety of malignancies, including acute myeloid leukemia (AML). Inhibition of Plk1 results in cell cycle arrest and apoptosis, and has anti-tumor effects in pre-clinical models. A number of Plk1 inhibitors have been developed, some of which have entered clinical trials. Of these, volasertib (BI6727) has been most extensively studied clinically in AML. Volasertib has demonstrated antileukemic activity in AML, both as a single agent and when combined with low-dose cytarabine. It is well tolerated, with the major toxicity being reversible myelosuppression. A recently completed phase III clinical trial in older AML patients will address the question of whether adding this agent to low-dose cytarabine is associated with a survival advantage.