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Updated: Jun 22, 2026
A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing (Neo)adjuvant Therapies
Published on: July 28, 2020
Efficacy of sunitinib and radiotherapy in genetically engineered mouse model of soft-tissue sarcoma
Sam S Yoon1, Lars Stangenberg, Yoon-Jin Lee
1Department of Surgery, Division of Surgical Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. syoon@partners.org
Purpose:
Sunitinib (SU) is a multitargeted receptor tyrosine kinase inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors. The present study examined SU and radiotherapy (RT) in a genetically engineered mouse model of soft tissue sarcoma (STS).
Methods And Materials:
Primary extremity STSs were generated in genetically engineered mice. The mice were randomized to treatment with SU, RT (10 Gy x 2), or both (SU+RT). Changes in the tumor vasculature before and after treatment were assessed in vivo using fluorescence-mediated tomography. The control and treated tumors were harvested and extensively analyzed.
Results:
The mean fluorescence in the tumors was not decreased by RT but decreased 38-44% in tumors treated with SU or SU+RT. The control tumors grew to a mean of 1378 mm(3) after 12 days. SU alone or RT alone delayed tumor growth by 56% and 41%, respectively, but maximal growth inhibition (71%) was observed with the combination therapy. SU target effects were confirmed by loss of target receptor phosphorylation and alterations in SU-related gene expression. Cancer cell proliferation was decreased and apoptosis increased in the SU and RT groups, with a synergistic effect on apoptosis observed in the SU+RT group. RT had a minimal effect on the tumor microvessel density and endothelial cell-specific apoptosis, but SU alone or SU+RT decreased the microvessel density by >66% and induced significant endothelial cell apoptosis.
Conclusion:
SU inhibited STS growth by effects on both cancer cells and tumor vasculature. SU also augmented the efficacy of RT, suggesting that this combination strategy could improve local control of STS.
Insights
Sunitinib (SU) combined with radiotherapy (RT) significantly inhibited soft tissue sarcoma (STS) growth in mice. This combination therapy demonstrated synergistic effects on cancer cell apoptosis and tumor vasculature, suggesting improved local control for STS.
Area of Science:
- Oncology
- Molecular Biology
- Medical Imaging
Background:
- Sunitinib (SU) is a receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors.
- Soft tissue sarcoma (STS) is a complex malignancy requiring effective therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of sunitinib (SU) and radiotherapy (RT) as monotherapies and in combination for soft tissue sarcoma (STS).
- To assess the impact of SU and RT on tumor vasculature and cancer cell apoptosis in a genetically engineered mouse model of STS.
Main Methods:
- Genetically engineered mice with primary extremity STSs were randomized into three groups: SU, RT, or SU+RT.
- Tumor vasculature changes were monitored using fluorescence-mediated tomography.
- Tumor growth, cell proliferation, apoptosis, and microvessel density were analyzed post-treatment.
Main Results:
- Sunitinib (SU) treatment, alone or combined with RT, decreased tumor fluorescence by 38-44%.
- Combination therapy (SU+RT) achieved maximal tumor growth inhibition (71%), significantly outperforming SU or RT alone.
- SU and SU+RT decreased tumor microvessel density by over 66% and induced endothelial cell apoptosis, while RT had minimal effect on vasculature.
Conclusions:
- Sunitinib effectively inhibits STS growth by targeting both cancer cells and tumor vasculature.
- The combination of sunitinib and radiotherapy demonstrates synergistic effects, enhancing apoptosis and improving tumor growth inhibition.
- This combination strategy holds promise for improving local control in soft tissue sarcoma treatment.
