• Samuel Abbou, Claudia Lanvers-Kaminsky, Estelle Daudigeos-Dubus, Ludivine LE Dret, Corinne Laplace-Builhe, Jan Molenaar, Gilles Vassal, Birgit Geoerger, and within the ITCC Biology and Preclinical Evaluation Committee.
• Vectorology and Anticancer Therapies, UMR 8203, CNRS, Paris-Sud University, Gustave Roussy Institute, Paris-Saclay University, Villejuif, France.
• Anticancer Res. 2016 Feb 1; 36 (2): 599-609.

BackgroundPolo-like kinase 1 (PLK1) controls the main cell-cycle checkpoints, suggesting utility of its inhibition for cancer treatment, including of highly proliferative pediatric cancer. This preclinical study explored the selective PLK1 inhibitor volasertib (BI 6727) alone and combined with chemotherapy in pediatric malignancies.Materials And MethodsInhibition of proliferation was explored in vitro using dimethylthiazol carboxymethoxyphenyl sulfophenyl tetrazolium (MTS) assay. Mice bearing human xenografts were treated with weekly intravenous injections of volasertib.ResultsVolasertib inhibited proliferation in all 40 cell lines tested, with a mean half-maximal growth inhibitory concentration of 313 nmol/l (range: 4-5000 nmol/l). Volasertib was highly active against RMS-1 alveolar rhabdomyosarcoma xenografts, resulting in 100% tumor regression. Activity was associated with complete and prolonged G2/M arrest and subsequent apoptotic cell death. Volasertib showed synergistic activity with vincristine but antagonistic effects with etoposide.ConclusionThese findings support the further exploration of volasertib for pediatric malignancies, particularly alveolar rhabdomyosarcoma, and its combination with mitotic spindle poison.Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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