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Oncotarget. 2019 Nov 5;10(60):6403-6417. doi: 10.18632/oncotarget.27237. eCollection 2019 Nov 5.

Volasertib preclinical activity in high-risk hepatoblastoma.

Author information

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.
#
Contributed equally

Abstract

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.

KEYWORDS:

PLK1; cell cycle; hepatoblastoma; liver; volasertib

Conflict of interest statement

CONFLICTS OF INTEREST The authors have no conflicts of interest with respect to the drugs used in this study.

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