Inhibition of DHODH Suppresses Tumor Growth in Medulloblastoma
Author Information
Author(s): Tsea Ioanna, Olsen Thale Kristin, Polychronopoulos Panagiotis Alkinoos, Tümmler Conny, Sykes David B., Baryawno Ninib, Dyberg Cecilia, Clark Geoffrey J.
Primary Institution: Karolinska Institutet
Hypothesis
Group 3 medulloblastoma could be sensitive to DHODH inhibition, and that DHODH inhibition may affect MYC expression.
Conclusion
Inhibiting DHODH with brequinar significantly reduces tumor growth and MYC expression in medulloblastoma.
Supporting Evidence
- High DHODH expression correlates with poor survival in group 3 medulloblastoma.
- BRQ demonstrated nanomolar efficacy in inducing apoptosis in group 3 MB cell lines.
- BRQ significantly inhibited tumor growth in a zebrafish model at non-toxic concentrations.
- MYC expression was significantly reduced following BRQ treatment in both cell lines.
Takeaway
This study shows that a drug called brequinar can help stop the growth of a type of brain tumor in kids by blocking a specific enzyme.
Methodology
The study used both in vitro cell line experiments and an in vivo zebrafish model to test the effects of brequinar on medulloblastoma.
Limitations
The study primarily focuses on group 3 medulloblastoma and may not be generalizable to other subtypes.
Statistical Information
P-Value
0.0028
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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