Targeting the Insulin Growth Factor and the Vascular Endothelial Growth Factor Pathways in Ovarian Cancer

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作者：

M Shao，S Hollar，D Chambliss，J Schmitt，R Emerson，B Chelladurai，S Perkins，M Ivan，D Matei

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摘要：

Antiangiogenic therapy is emerging as a highly promising strategy for the treatment of , but the clinical benefits are usually transitory. The purpose of this study was to identify and target alternative angiogenic pathways that are upregulated in ovarian xenografts during treatment with bevacizumab. For this, -focused gene expression arrays were used to measure gene expression levels in SKOV3 and A2780 serous ovarian xenografts treated with bevacizumab or control. -was used for results validation. The growth factor 1 () was found upregulated in and stromal cells in the two ovarian treated with bevacizumab. Cixutumumab was used to block signaling in vivo. Dual anti-and blockade with bevacizumab and cixutumumab resulted in increased inhibition of . Immunohistochemistry measured multivessel density, activation, and , whereas terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay measured in xenografts. Bevacizumab and cixutumumab combination increased cell in vivo compared with therapy targeting either individual pathway. The combination blocked and but not more significantly than each antibody alone. In summary, activation represents an important mechanism of adaptive escape during anti-therapy in . This study provides the rationale for designing bevacizumab-based combination regimens to enhance antitumor activity.

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关键词：

prostate cancer androgen deprivation radiotherapy

DOI：

10.1158/1535-7163.MCT-11-0961

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年份：

2012