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Inhibition of tumor growth in a human neuroblastoma xenograft model with TNP-470
S Shusterman1, S A Grupp, J M Maris
1Division of Oncology, The Children's Hospital of Philadelphia, and Department of Pediatrics, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4318, USA. shusterman@email.chop.edu
Unlabelled:
Background and Procedure High-risk neuroblastoma disease features are correlated with tumor vascularity, suggesting that angiogenesis inhibitors may be a useful addition to current therapeutic strategies. We therefore examined the efficacy of TNP-470 (TAP Pharmaceuticals, Deerfield, IL) in human neuroblastoma xenograft models.
Results:
Tumor growth rate was markedly inhibited in mice receiving TNP-470 administered alone with a treatment to control ratio (T/C) at day 21 = 0.4 (P <.001). TNP-470 also significantly inhibited tumorigenicity when administered shortly after xenograft inoculation (T/C at day 30 = 0.1, P <.001) and when administered following cyclophosphamide (T/C at day 35 = 0.1, P <.001).
Conclusions:
These data show that TNP-470 is a potent inhibitor of human neuroblastoma growth both alone and when given with conventional chemotherapy, suggesting that it may be a useful adjunctive therapy for high-risk neuroblastoma patients.
Insights
The anti-angiogenesis drug TNP-470 effectively inhibits human neuroblastoma growth in preclinical models. This agent shows promise as an adjunctive therapy for high-risk neuroblastoma patients when combined with chemotherapy.
Area of Science:
- Oncology
- Pharmacology
Background:
- High-risk neuroblastoma is associated with tumor vascularity.
- Angiogenesis inhibitors are potential therapeutic agents for neuroblastoma.
Purpose of the Study:
- To evaluate the efficacy of TNP-470 in human neuroblastoma xenograft models.
Main Methods:
- Administration of TNP-470 to mice with human neuroblastoma xenografts.
- Assessment of tumor growth inhibition and tumorigenicity.
Main Results:
- TNP-470 significantly inhibited tumor growth (T/C = 0.4 at day 21).
- TNP-470 demonstrated potent inhibition when administered alone or with cyclophosphamide (T/C = 0.1 at days 30 and 35).
Conclusions:
- TNP-470 is a potent inhibitor of human neuroblastoma growth.
- TNP-470 may serve as a valuable adjunctive therapy for high-risk neuroblastoma.