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Updated: May 10, 2025
Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
Published on: December 26, 2016
Functional screening identifies kinesin spindle protein inhibitor filanesib as a potential treatment option for
Ruth Nousiainen1,2,3, Katja Eloranta4,5,6, Jani Saarela2
1Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
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.
Insights
Filanesib, a Kinesin Spindle Protein (KSP) inhibitor, shows promise for treating hepatoblastoma, a rare pediatric liver cancer. This drug effectively reduced tumor growth in preclinical models, suggesting its potential for clinical trials.
Area of Science:
- Oncology
- Pharmacology
- Pediatric Medicine
Background:
- Hepatoblastoma is a rare pediatric liver malignancy.
- Current treatments include surgery and chemotherapy.
- Novel therapeutic strategies are needed for aggressive hepatoblastoma.
Purpose of the Study:
- To identify novel therapeutic agents for hepatoblastoma.
- To evaluate the efficacy of the KSP inhibitor filanesib in hepatoblastoma models.
Main Methods:
- Drug screening of 527 compounds across six hepatoblastoma cell models and healthy hepatocytes.
- In vitro evaluation of filanesib, including cell cycle arrest and apoptosis assays.
- In vivo assessment of filanesib efficacy in four hepatoblastoma mouse models.
Main Results:
- 98 compounds showed cancer-selective activity; filanesib was effective in all hepatoblastoma models.
- Filanesib induced G2/M arrest and apoptosis in hepatoblastoma cells at safe concentrations.
- Filanesib significantly reduced tumor growth in 4/5 mouse models, with one showing complete growth arrest.
Conclusions:
- Filanesib demonstrates significant preclinical efficacy against hepatoblastoma.
- Filanesib represents a potential therapeutic candidate for hepatoblastoma.
- Further clinical investigation of filanesib for hepatoblastoma treatment is warranted.
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