Yoon, SamStangenberg, LarsLee, Yoon-JinRothrock, CourtneyDreyfuss, JonathanBaek, Kwan-HyuckWaterman, PeterNielsen, G. PeturWeissleder, RalphMahmood, UmarPark, PeterJacks, TylerDodd, RebeccaFisher, CarolynRyeom, SandraKirsch, David2019-09-212009Yoon, Sam S., Lars Stangenberg, Yoon-Jin Lee, Courtney Rothrock, Jonathan M. Dreyfuss, Kwan-Hyuck Baek, Peter R. Waterman, et al. 2009. “Efficacy of Sunitinib and Radiotherapy in Genetically Engineered Mouse Model of Soft-Tissue Sarcoma.” International Journal of Radiation Oncology*Biology*Physics 74 (4): 1207–16. https://doi.org/10.1016/j.ijrobp.2009.02.052.0360-30161879-355Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41384316Purpose: 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.en-USJournal Article2019-09-2110.1016/j.ijrobp.2009.02.052