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Int J Radiat Oncol Biol Phys. 2009 Jul 15;74(4):1207-16. doi: 10.1016/j.ijrobp.2009.02.052.

Efficacy of sunitinib and radiotherapy in genetically engineered mouse model of soft-tissue sarcoma.

Author information

  • 1Department of Surgery, Division of Surgical Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. syoon@partners.org

Erratum in

  • Int J Radiat Oncol Biol Phys. 2010 Aug 1;77(5):1607.

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.

PMID:
19545786
[PubMed - indexed for MEDLINE]
PMCID:
PMC2733223
Free PMC Article

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