November 1 Clinical Cancer Research Highlights

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Selected Articles from the November 1, 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 Clinical Cancer Research is published. Click on the article title to view the complete article.

View the Table of Contents for the November 1 issue of Clinical Cancer Research.

Novel Cancer-testis Antigen CRT2 Identified

Inhibition of Hsp90 Reduces Pancreatic Cancer Growth

Heat-shock-protein 90 (Hsp90) is an important chaperone required for stability of multiple oncogenic proteins. The study by Lang and colleagues demonstrated that Hsp90 inhibitors could be used for molecular targeted therapy in treating pancreatic cancer. The authors provided evidence that Hsp90 antagonists directly inhibit IGF-IR phosphorylation, in addition to disrupting IL-6/STAT3 proangiogenic signalling cascades, and they also identified a novel IL-6/HIF-1α/STAT3 autocrine loop in pancreatic cancer. Inhibition of Hsp90 led to a significant reduction in pancreatic tumor growth and vascularization in an orthotopic model, and this effect was in part mediated through down-regulation of IGF-IR and STAT3 activation in tumors. 

Defucosylated anti-CCR4 mAb as a Novel Therapy for CTCL

Targeting of tumor antigens applying monoclonal antibodies to patients represents a successful strategy in oncology. An important target is the carcinoembryonic antigen (CEA), overexpressed by the majority of mammalian cancers. To translate passive immunotherapy into an active immunization regimen, Brämswig and colleagues applied the mimotope technique. Using monoclonal anti-CEA antibody Col-1, they selected peptides from phage libraries. Being epitope mimics, the synthetic mimotopes induced anti-CEA antibodies in BALB/c mice with cytotoxic potential in vitro and in a xenogenic tumor transplant model in vivo. Thus, mimotopes are suitable tools for anti-cancer vaccination and possibly open a new era of tumor immunotherapy.