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Antiangiogenic therapy inhibits human neuroblastoma growth
H M Katzenstein1, H R Salwen, N N Nguyen
1Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School and Children's Memorial Hospital, Chicago, Illinois 60614, USA.
Background:
Angiogenesis plays a crucial role in the progression and metastasis of malignant solid tumors. In many types of cancer, including neuroblastoma, high tumor vascularity correlates with poor outcome. Recently, a number of angiogenic inhibitors have been identified that had antitumor activity in preclinical studies.
Procedure:
To investigate the effect of the antiangiogenic agent TNP-470 on neuroblastoma tumor growth, we treated nude mice with TNP-470 after they were inoculated subcutaneously with 5 x 10(6) cells from the MYCN-amplified, human neuroblastoma cell line NBL-W-N.
Results:
TNP-470 did not significantly affect tumor growth when it was administered to mice with large tumors (>600 mm3). However, when TNP-470 was administered in the setting of microscopic disease 12 hr following tumor cell inoculation, treated mice had a significantly improved tumor-free survival at 12 weeks (P < 0.001), and overall survival at 45 weeks (P < 0.001), compared to control animals.
Conclusions:
Our studies suggest that TNP-470 treatment may be most effective if it is administered in the setting of microscopic disease. We speculate that TNP-470 may inhibit neuroblastoma growth in children if treatment is initiated following intensive multimodality therapy, when residual disease is minimal.
Insights
Early TNP-470 treatment significantly improved survival in neuroblastoma models with microscopic disease. This antiangiogenic agent shows promise for treating minimal residual disease in children.
Area of Science:
- Oncology
- Cancer Research
- Angiogenesis Inhibition
Background:
- Angiogenesis is vital for solid tumor progression and metastasis.
- High tumor vascularity in cancers like neuroblastoma correlates with poor prognosis.
- Antiangiogenic agents show preclinical antitumor activity.
Purpose of the Study:
- To evaluate the efficacy of the antiangiogenic agent TNP-470 against neuroblastoma.
- To determine the impact of TNP-470 on neuroblastoma tumor growth and survival.
Main Methods:
- Nude mice were inoculated with human neuroblastoma cells (NBL-W-N).
- Mice received TNP-470 treatment at different stages of tumor development (large tumors vs. microscopic disease).
Main Results:
- TNP-470 did not significantly inhibit growth in mice with large tumors (>600 mm3).
- Administration of TNP-470 for microscopic disease resulted in significantly improved tumor-free survival (12 weeks) and overall survival (45 weeks) compared to controls (P < 0.001).
Conclusions:
- TNP-470 efficacy appears dependent on early administration during microscopic disease.
- This suggests TNP-470 could be beneficial in pediatric neuroblastoma if initiated after intensive therapy when disease is minimal.