Volasertib preclinical activity in high-risk hepatoblastoma
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Dina Kats1, Cora A. Ricker1, Noah E. Berlow1, Bénédicte Noblet2, Delphine Nicolle2, Katell Mevel2, Sophie Branchereau3, Jean-Gabriel Judde2, Cody D. Stiverson1, Christina L. Stiverson1, Matthew N. Svalina1, Teagan Settelmeyer1, Kevin Matlock4, Melvin Lathara4, Charlotte Mussini2, James I. Geller5, Christopher Noakes6, Ido Sloma6, Narendra Bharathy1, Stefano Cairo2,* and Charles Keller1,*
1 Children’s Cancer Therapy Development Institute, Beaverton, OR, USA
2 Research and Development Unit, XenTech, Evry, France
3 Bicêtre Hospital, Le Kremlin Bicêtre, France
4 Omics Data Automation, Beaverton, OR, USA
5 Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
6 Champions Oncology, Rockville, MD, USA
* These authors contributed equally to this work
|Stefano Cairo,||email:||[email protected]|
|Charles Keller,||email:||[email protected]|
Keywords: hepatoblastoma; PLK1; volasertib; liver; cell cycle
Received: April 16, 2019 Accepted: August 12, 2019 Published: November 05, 2019
Relapsed and metastatic hepatoblastoma represents an unmet clinical need with limited chemotherapy treatment options. In a chemical screen, we identified volasertib as an agent with in vitro activity, inhibiting hepatoblastoma cell growth while sparing normal hepatocytes. Volasertib targets PLK1 and prevents the progression of mitosis, resulting in eventual cell death. PLK1 is overexpressed in hepatoblastoma biopsies relative to normal liver tissue. As a potential therapeutic strategy, we tested the combination of volasertib and the relapse-related hepatoblastoma chemotherapeutic irinotecan. We found both in vitro and in vivo efficacy of this combination, which may merit further preclinical investigation and exploration for a clinical trial concept.
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