Cediranib/AZD2171 Inhibits Bone and Brain Metastasis in a Preclinical Model of Advanced Prostate Cancer

被引:42
|
作者
Yin, Juan Juan
Zhang, Luhua
Munasinghe, Jeeva [2 ]
Linnoila, R. Ilona
Kelly, Kathleen [1 ]
机构
[1] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA
[2] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging & Mouse Imaging Facil, NIH, Bethesda, MD USA
关键词
TYROSINE KINASE INHIBITOR; ANTIANGIOGENIC THERAPY; TUMOR VASCULATURE; VEGF INHIBITORS; CELLS; GROWTH; ANGIOGENESIS; PROGRESSION; MECHANISMS; PROMOTES;
D O I
10.1158/0008-5472.CAN-10-1435
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Late stage or aggressive cancers exhibit metastatic growth at multiple sites, and the characterization of treatment response in various organs to drugs with potentially wide-ranging efficacy is needed. Tumor cells that induce angiogenesis are a common characteristic of metastatic disease, and clinically, antiangiogenic therapies have shown value in the setting of advanced cancer. However, recent preclinical studies have suggested that exposure to antiangiogenic drugs can increase tumor invasiveness and metastasis, making it important to determine which contexts antiangiogenic therapy is most appropriate. We describe here the effects of cediranib, a receptor tyrosine kinase inhibitor, in a model of advanced prostate cancer metastatic to skeleton and brain. Treatment with cediranib decreased metastatic tumor burden in the brain and bone, decreased cerebral vasogenic edema, and improved survival, despite increasing the invasive histology of brain metastases. Short-duration cediranib treatment given at the time of tumor cell dissemination was sufficient to inhibit the establishment and subsequent growth of bone metastases, although brain metastases were subject to rebound growth after the discontinuation of cediranib. Distinct growth patterns at different organ sites in the same animal showed that certain tumor microenvironments such as bone may be most amenable to interventions by anti-vascular endothelial growth factor (VEGF) therapies. In addition, anti-VEGF treatment may be of utility in decreasing the rapid growth of solid brain metastases and vasogenic edema in patients with advanced cancer, leading to reduced morbidity and associated clinical benefit. Cancer Res; 70(21); 8662-73. (C)2010 AACR.
引用
收藏
页码:8662 / 8673
页数:12
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