@article {153001, title = {Efficacy of sunitinib and radiotherapy in genetically engineered mouse model of soft-tissue sarcoma.}, journal = {Int J Radiat Oncol Biol Phys}, volume = {74}, number = {4}, year = {2009}, month = {2009 Jul 15}, pages = {1207-16}, abstract = { 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. }, keywords = {Angiogenesis Inhibitors, Animals, Antineoplastic Agents, Combined Modality Therapy, Drug Screening Assays, Antitumor, Indoles, Mice, Mice, Transgenic, Pyrroles, Random Allocation, Receptor, Platelet-Derived Growth Factor beta, Sarcoma, Vascular Endothelial Growth Factor Receptor-2}, issn = {1879-355X}, doi = {10.1016/j.ijrobp.2009.02.052}, author = {Yoon, Sam S and Stangenberg, Lars and Lee, Yoon-Jin and Rothrock, Courtney and Dreyfuss, Jonathan M and Baek, Kwan-Hyuck and Waterman, Peter R and Nielsen, G Petur and Weissleder, Ralph and Mahmood, Umar and Park, Peter J and Jacks, Tyler and Dodd, Rebecca D and Fisher, Carolyn J and Ryeom, Sandra and Kirsch, David G} }