PT  - JOURNAL ARTICLE
AU  - Dorothea Rudolph
AU  - Maria Antonietta Impagnatiello
AU  - Claudia Blaukopf
AU  - Christoph Sommer
AU  - Daniel W. Gerlich
AU  - Mareike Roth
AU  - Ulrike Tontsch-Grunt
AU  - Andreas Wernitznig
AU  - Fabio Savarese
AU  - Marco H. Hofmann
AU  - Christoph Albrecht
AU  - Lena Geiselmann
AU  - Markus Reschke
AU  - Pilar Garin-Chesa
AU  - Johannes Zuber
AU  - Jürgen Moll
AU  - Günther R. Adolf
AU  - Norbert Kraut
TI  - Efficacy and Mechanism of Action of Volasertib, a Potent and Selective Inhibitor of Polo-Like Kinases, in Preclinical Models of Acute Myeloid Leukemia
AID  - 10.1124/jpet.114.221150
DP  - 2015 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 579--589
VI  - 352
IP  - 3
4099  - http://jpet.aspetjournals.org/content/352/3/579.short
4100  - http://jpet.aspetjournals.org/content/352/3/579.full
SO  - J Pharmacol Exp Ther2015 Mar 01; 352
AB  - 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.