June 15 Cancer Research Highlights

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Selected Articles from the June 15, 2007 Issue

The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the June 15 issue of Cancer Research.

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New Serum Markers Detect Colorectal Cancer

Leman et al.

Page 5600

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Peritoneal Inflammation Facilitates Ovarian Tumor Metastasis

Robinson-Smith et al.
Page 5708

The tumor microenvironment is known to have a profound impact on tumor progression in a highly cell and organ context-specific manner. Robinson-Smith et al. investigated whether peritoneal inflammation plays a causative role in ovarian tumor metastasis, a poorly understood process. The authors concluded that localized inflammation facilitates ovarian tumor metastasis by a mechanism largely mediated by macrophages. These processes may involve stromal cell production of vascular endothelial growth factor. The finding that innate immunity accelerates tumor spread, and that macrophages are largely responsible for progression, provides a potential new stromal target for delaying peritoneal metastasis.

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Targeting Tumor α_vβ₃ Integrin Prevents Bone Metastasis 

Zhao et al.
Page 5821

In breast cancer bone metastasis, tumor cells stimulate osteoclast-mediated bone resorption, and bone-derived growth factors released from resorbed bone stimulate tumor growth. The α_vβ₃ integrin is an adhesion receptor expressed by breast cancer cells and osteoclasts, and is implicated in tumor cell invasion and osteoclast-mediated bone resorption. Zhao et al. hypothesized that the therapeutic targeting of tumor α_vβ₃ integrin would prevent bone metastasis formation. They found that a short-term treatment with a specific inhibitor, PSK1404, alters the homing of tumor cells to bone, whereas continuous PSK1404 treatment also inhibits osteoclast-mediated bone resorption. Thus, tumor α_vβ₃ integrin is a therapeutic target for the prevention of skeletal metastases in breast cancer.

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New Phosphatidylinositide 3-Kinase Inhibitor Characterized

Raynaud et al.

Page 5840

Extensive evidence implicates activation of the lipid phosphatidylinositide 3-kinase (PI3K) pathway in the genesis and progression of various human cancers, making it an attractive drug target. Raynaud et al. have characterized the pharmacologic properties of a prototype of a new series of inhibitors of class I PI3K. The small molecule PI103 is a potent inhibitor with low IC₅₀ values against recombinant PI3K isoforms. The authors demonstrated inhibition of invasion in orthotopic breast and ovarian cancer xenograft models and obtained evidence that PI103 also has antiangiogenic potential. Despite its rapid in vivo metabolism, PI103 is a valuable compound for exploring the biological function of class I PI3K, and is a clear lead for further optimization of this novel class of targeted therapeutics.

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AIB1 Expression Induces Prostate Cancer Progression

Chung et al.
Page 5965

Although the amplified-in-breast cancer 1 (AIB1, SRC-3, ACTR, or NCoA3) was defined as a coactivator for androgen receptor (AR) by in vitro studies, its role in AR-mediated prostate development and prostate cancer remained unexplored. Chung et al. have reported that AIB1 is expressed in the basal and stromal cells, but not in the epithelial cells of normal mouse prostates. Their results indicated that induction of AIB1 expression in partially transformed epithelial cells is essential for progression of prostate tumorigenesis into poorly differentiated carcinoma. Inhibition of AIB1 expression or function in the prostate epithelium may be a potential strategy to suppress prostate cancer initiation and progression.

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