August 15 Clinical Cancer Research Highlights

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Selected Articles from the August 15, 2008 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 Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the August 15 issue of Clinical Cancer Research.

The Chemokine SDF1 Implicated in Adenoma

Cytokines control pituitary development, function and cell division. Barbieri and colleagues analyzed the role of the chemokine SDF1 and its receptor CXCR4 in human adenoma and normal pituitaries. They observed overexpression of CXCR4 and SDF1 mRNA and co-expression of CXCR4 and SDF1 protein in adenoma cells derived from human tumors. In subsets of normal anterior pituitary cells, they also identified some CXCR4 and SDF1 co-expressing cells, and these tended to be found in discrete areas of cells secreting prolactin, ACTH, and GH. Additionally, they found that in pituitary adenoma primary cultures, SDF1 could increase DNA synthesis. These findings implicate the CXCR4/SDF1 chemokine network in pituitary adenoma proliferation and suggest that it may be a novel therapeutic target. 

NPY Receptor Expression in Human Sarcomas

Treatment of Adenoid Cystic Carcinoma with Vandetanib

The development of effective systemic therapeutic agents is a goal in adenoid cystic carcinoma (ACC) treatment. Choi and colleagues evaluated whether vandetanib, a potent inhibitor of VEGFR-2 and EGFR tyrosine kinases, had anti-tumor efficacy in vitro and in a mouse model of human ACC. They found that vandetanib caused dose-dependent inhibition of VEGFR-2 and EGFR phosphorylation, and it inhibited proliferation and induced apoptosis of ACC cells in vitro. Further, vandetanib decreased tumor volumes significantly in an orthotopic nude mouse model of human ACC. These results suggest that vandetanib is a promising agent for the treatment of ACC.

The EFGR family member HER3 is overexpressed in many human cancers and has been associated with poor prognosis. To investigate the role of HER3 in melanoma, Reschke and colleagues examined HER3 protein expression in primary malignant melanoma and metastases using tissue microarrays. They found that HER3 was highly expressed in melanoma and high HER3 expression levels correlated with disease progression and reduced patient survival. Additionally, in vitro experiments showed that HER3 monoclonal antibodies can inhibit HER3 activation and reduce melanoma cell proliferation, migration, and invasion. These results provide new insights into the role of HER3 in melanoma and suggest new possibilities for therapeutic intervention.