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Initial in vivo testing of a multitarget kinase inhibitor, regorafenib, by the Pediatric Preclinical Testing
Douglas J Harrison1, Jonathan D Gill1, Michael E Roth1
1Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, Texas.
Background:
Regorafenib is a small molecule multikinase inhibitor that inhibits multiple kinases including BRAF, KIT, PDGFRB, RAF, RET, and VEGFR1-3.
Procedures:
The in vivo anticancer effects of regorafenib were assessed in a panel of six osteosarcoma models, three rhabdomyosarcoma models, and one Ewing sarcoma model.
Results:
Regorafenib induced modest inhibition of tumor growth in the models evaluated.
Conclusion:
The overall pattern of response to regorafenib appears similar to that of the kinase inhibitor sorafenib, with pronounced slowing of tumor growth in some models, limited to the period of agent administration, being the primary treatment effect.
Insights
Regorafenib, a multikinase inhibitor, showed modest tumor growth inhibition in pediatric sarcoma models. Its effects were temporary, similar to sorafenib, highlighting the need for further research in sarcoma treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Regorafenib is a small molecule multikinase inhibitor targeting BRAF, KIT, PDGFRB, RAF, RET, and VEGFR1-3.
- Understanding its efficacy in various sarcoma types is crucial for potential therapeutic applications.
Purpose of the Study:
- To evaluate the in vivo anticancer effects of regorafenib.
- To assess the efficacy of regorafenib in osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma models.
Main Methods:
- In vivo assessment of regorafenib's anticancer effects.
- Utilized six osteosarcoma, three rhabdomyosarcoma, and one Ewing sarcoma models.
Main Results:
- Regorafenib demonstrated modest inhibition of tumor growth across the evaluated models.
- The primary treatment effect observed was a pronounced slowing of tumor growth during agent administration.
Conclusions:
- The response pattern to regorafenib is comparable to that of sorafenib.
- Regorafenib's tumor growth inhibition is limited to the period of administration, suggesting a need for optimized treatment strategies.