Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma
Hepatoblastoma is a rare pediatric liver malignancy usually treated with surgery and chemotherapy. To explore new treatment options for hepatoblastoma, drug screening was performed using six cell models established from aggressive hepatoblastoma tumors and healthy pediatric primary hepatocytes. Of the 527 screened compounds, 98 demonstrated cancer-selective activity in at least one hepatoblastoma model. The kinesin spindle protein (KSP) inhibitor filanesib was effective in all models and was further evaluated. Filanesib induced G2/M arrest and apoptosis in hepatoblastoma cells at concentrations tolerable to primary hepatocytes. Prominent nuclear fragmentation was observed in filanesib-treated hepatoblastoma cells. Genes participating in cell cycle regulation were noted to be differentially expressed after filanesib treatment. Filanesib reduced the rate of tumor growth in 4/5 hepatoblastoma mice models. One of these models showed complete growth arrest. Our results suggest that filanesib is a potential candidate for hepatoblastoma treatment and should be investigated in future clinical trials.
Authors
- Tamara J. Luck (ORCID: https://orcid.org/0000-0002-9859-1261)
- Émilie Indersie (ORCID: https://orcid.org/0000-0001-8974-6551)
- David Brown Wilson (ORCID: https://orcid.org/0000-0002-1826-7745)
- Ruth Nousiainen (ORCID: https://orcid.org/0000-0001-5811-1262)
- Marjut Pihlajoki (ORCID: https://orcid.org/0000-0002-9869-5706)
- Katja Eloranta (ORCID: https://orcid.org/0000-0002-0396-5137)
- Antti Hassinen (ORCID: https://orcid.org/0000-0001-9491-2868)
- Lassi Paavolainen (ORCID: https://orcid.org/0000-0003-1508-2718)
- Swapnil Potdar (ORCID: https://orcid.org/0000-0002-2778-6918)
- Jani Saarela (ORCID: https://orcid.org/0000-0001-7306-7175)
- Stefano Cairo (ORCID: https://orcid.org/0000-0002-4725-5970)
- Markku Heikinheimo
- Michaela Feodoroff (ORCID: https://orcid.org/0000-0002-6094-9838)
- Vilja Pietiäinen (ORCID: https://orcid.org/0000-0003-3125-2406)
- Jouko Lohi
Institutions
- University of Helsinki (FI)
- Tampere University (FI)
- Washington University in St. Louis (US)
- Helsinki University Hospital (FI)
- Helsinki Children's Hospital (FI)
- Institute for Molecular Medicine Finland (FI)
- Champions Oncology (United States) (US)
- Città della Speranza Foundation (IT)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-04-25
- DOI
- https://doi.org/10.1038/s41698-025-00915-8
- Citations
- 2
- Primary Topic
- Microtubule and mitosis dynamics
- Type
- article
- Field-Weighted Citation Impact
- 2.30
Funders
- Helsingin Yliopisto
- Helsingin ja Uudenmaan Sairaanhoitopiiri
- Academy of Finland
- Suomen Kulttuurirahasto
- Päivikki ja Sakari Sohlbergin Säätiö
- Emil Aaltosen Säätiö
- Sigrid Juséliuksen Säätiö
- Syöpäsäätiö
- Biocenter Finland
- Helsinki Institute of Life Science, Helsingin Yliopisto
- Kymenlaakson Rahasto