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. 2019 Nov 22;9:1271. doi: 10.3389/fonc.2019.01271

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Copyright © 2019 Gatz, Aladowicz, Casanova, Chisholm, Kearns, Fulda, Geoerger, Schäfer and Shipley.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Model for the effects of the combination of PLK1 inhibitors BI2536 or BI6727 (volasertib) plus the microtubule disrupter vincristine (VCR) on rhabdomyosarcoma cells. Inhibition of PLK1 and vincristine disrupts mitosis which in combination can synergistically lead to apoptosis. PLK1 inhibition also affects the phosphorylation of the PAX3-FOXO1 (P3F) protein and MYCN either indirectly via P3F loss and/or directly via its phosphorylation status, and may additionally contribute to the effects of these inhibitors in fusion positive rhabdomyosarcomas. Dashed and solid lines, represent proven and plausible links and effects in rhabdomyosarcoma models, respectively.