2. Academic Validation
  3. Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma

Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma

  • NPJ Precis Oncol. 2025 Apr 25;9(1):122. doi: 10.1038/s41698-025-00915-8.
Ruth Nousiainen 1 2 3,  Katja Eloranta 4 5 6,  Jani Saarela 2,  Antti Hassinen 2,  Tamara J Luck 2 3,  Stefano Cairo 7 8 9,  Emilie Indersie 7,  Swapnil Potdar 2,  Michaela J Feodoroff 2 3,  Jouko Lohi 10,  Lassi Paavolainen 2 3,  David B Wilson 11 12,  Vilja Pietiäinen 2 3,  Markku Heikinheimo 1 12 13,  Marjut Pihlajoki 1
Affiliations

Affiliations

  • 1 Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • 2 Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.
  • 3 iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
  • 4 Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. katja.eloranta@helsinki.fi.
  • 5 Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland. katja.eloranta@helsinki.fi.
  • 6 iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland. katja.eloranta@helsinki.fi.
  • 7 XenTech, Evry, France.
  • 8 Champions Oncology, Hackensack, NJ, USA.
  • 9 Istituto di Ricerca Pediatrica, Padova, Italy.
  • 10 Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • 11 Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.
  • 12 Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
  • 13 Faculty of Medicine and Health Technology, Center for Child, Adolescent, and Maternal Health Research, Tampere University, Tampere, Finland.
PMID: 40281281 DOI: 10.1038/s41698-025-00915-8
Abstract

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.

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