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Published on: July 20, 2019
Ribavirin as a potential therapeutic for atypical teratoid/rhabdoid tumors
Joshua Casaos1, Sakibul Huq1, Tarik Lott1
1Hunterian Neurosurgical Research Laboratory, Neurosurgery Department, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA.
Abstract:
Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive, malignant tumors and are the most common malignant brain tumor in children under 6 months of age. Currently, there is no standard treatment for AT/RT. Recent studies have reported potential anti-tumoral properties of ribavirin, a guanosine analog and anti-viral molecule approved by the Food and Drug Administration for treatment of hepatitis C. We previously demonstrated that ribavirin inhibited glioma cell growth in vitro and in vivo. Based on these results and the fact that no pre-clinical model of ribavirin in AT/RT exists, we decided to investigate the effect of ribavirin on several human AT/RT cell lines (BT12, BT16, and BT37) both in vitro and in vivo. We provide evidence that ribavirin has a significant impact on AT/RT cell growth and increases cell cycle arrest and cell death, potentially through modulation of the eIF4E and/or EZH2 pathways. Interestingly, using scratch wound and transwell Boyden chamber assays, we observed that ribavirin also impairs AT/RT cell migration, invasion, and adhesion. Finally, we demonstrate that ribavirin significantly improves the survival of mice orthotopically implanted with BT12 cells. Our work establishes that ribavirin is effective against AT/RT by decreasing tumoral cell growth and dissemination and could represent a new therapeutic option for children with this deadly disease.
Insights
Ribavirin shows promise in treating atypical teratoid/rhabdoid tumors (AT/RT), a rare pediatric brain cancer. This study found ribavirin inhibits AT/RT cell growth, migration, and improves survival in preclinical models.
Area of Science:
- Pediatric neuro-oncology
- Cancer pharmacology
- Molecular oncology
Background:
- Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive pediatric brain cancers with no standard treatment.
- Ribavirin, an antiviral drug, has demonstrated anti-tumoral properties in other cancers.
Purpose of the Study:
- To investigate the efficacy of ribavirin against human AT/RT cell lines.
- To evaluate ribavirin's impact on AT/RT cell growth, migration, and survival in preclinical models.
Main Methods:
- Treatment of human AT/RT cell lines (BT12, BT16, BT37) with ribavirin in vitro.
- Assessment of cell cycle, cell death, migration, invasion, and adhesion.
- Evaluation of ribavirin's effect on survival in mice with orthotopic AT/RT xenografts.
Main Results:
- Ribavirin significantly inhibited AT/RT cell growth, induced cell cycle arrest, and promoted cell death.
- Ribavirin reduced AT/RT cell migration, invasion, and adhesion.
- Ribavirin treatment significantly improved survival in a mouse model of AT/RT.
Conclusions:
- Ribavirin demonstrates significant anti-tumoral activity against AT/RT.
- Ribavirin's mechanisms may involve modulation of eIF4E and/or EZH2 pathways.
- Ribavirin represents a potential novel therapeutic strategy for AT/RT.
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