Abstract
Polo-like kinase 1 (Plk1), a member of the Polo-like kinase family of serine/threonine kinases, is a key regulator of multiple steps in mitosis. Here we report on the pharmacological profile of volasertib, a potent and selective Plk inhibitor, in multiple preclinical models of acute myeloid leukemia (AML) including established cell lines, bone marrow samples from AML patients in short-term culture, and subcutaneous as well as disseminated in vivo models in immune-deficient mice. Our results indicate that volasertib is highly efficacious as a single agent and in combination with established and emerging AML drugs, including the antimetabolite cytarabine, hypomethylating agents (decitabine, azacitidine), and quizartinib, a signal transduction inhibitor targeting FLT3. Collectively, these preclinical data support the use of volasertib as a new therapeutic approach for the treatment of AML patients, and provide a foundation for combination approaches that may further improve and prolong clinical responses.
Footnotes
- Received October 29, 2014.
- Accepted January 5, 2015.
D.R., A.W., C.A., L.G., U.T.-G., M.A.I., P.G.-C., J.M., F.S., M.R., G.R.A., and N.K. are employees of Boehringer Ingelheim. D.W.G., C.B., and C.S. are employees of the Institute of Molecular Biotechnology, Austrian Academy of Sciences, and received funding for their research from Boehringer Ingelheim.
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- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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