Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma
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 hepatocy...
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Nature Portfolio
2025-04-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00915-8 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ruth Nousiainen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5ac5578eeef4411f9cfd2f356a013c05 |
| institution | OA Journals |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-5ac5578eeef4411f9cfd2f356a013c052025-08-20T02:19:58ZengNature Portfolionpj Precision Oncology2397-768X2025-04-019111810.1038/s41698-025-00915-8Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastomaRuth Nousiainen0Katja Eloranta1Jani Saarela2Antti Hassinen3Tamara J. Luck4Stefano Cairo5Emilie Indersie6Swapnil Potdar7Michaela J. Feodoroff8Jouko Lohi9Lassi Paavolainen10David B. Wilson11Vilja Pietiäinen12Markku Heikinheimo13Marjut Pihlajoki14Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University HospitalPediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University HospitalInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiXenTechXenTechInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiDepartment of Pathology, University of Helsinki and Helsinki University HospitalInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiDepartment of Developmental Biology, Washington University School of MedicineInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of HelsinkiPediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University HospitalPediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University HospitalAbstract 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.https://doi.org/10.1038/s41698-025-00915-8 |
| spellingShingle | 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 Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma npj Precision Oncology |
| title | Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma |
| title_full | Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma |
| title_fullStr | Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma |
| title_full_unstemmed | Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma |
| title_short | Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma |
| title_sort | functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for hepatoblastoma |
| url | https://doi.org/10.1038/s41698-025-00915-8 |
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