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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月25日

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  • Ruth Nousiainen,
  • Katja Eloranta,
  • Jani Saarela,
  • Antti Hassinen,
  • Tamara J. Luck,
  • Stefano Cairo,
  • Emilie Indersie,
  • Swapnil Potdar,
  • Michaela J. Feodoroff,
  • Jouko Lohi,
  • Lassi Paavolainen,
  • David B. Wilson,
  • Vilja Pietiäinen,
  • Markku Heikinheimo,
  • Marjut Pihlajoki

摘要

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.