September 15 Clinical Cancer Research Highlights

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Selected Articles from the September 15, 2006 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 September 15 issue of Clinical Cancer Research.

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Premiere of CCR Focus

Predictive Preclinical Models of Human Cancer: Mouse Models Get Another Chance

Guest Editor: Cory Abate-Shen
Pages 5273-5328

CCR Focus, premiering in this issue, is devoted to the topic of mouse models. Guest Editor Cory Abate-Shen invited a series of stimulating reviews that describe the benefits of using mouse models to study human cancer and the potential impact of these models for the treatment of patients with cancer. Each review is written by experts both in the generation of mouse models of cancer, as well as in the application of such models for translational research. All five reviews describe a new generation of genetically engineered mouse models that accurately recapitulate many features of human cancer and thereby provide valuable opportunities for drug discovery and other translational applications. Clinical Cancer Research developed CCR Focus with the hope that this series will educate the interested non-expert and stimulate interest, encouragement, and inspiration for those in the field.

• Editor's Note: Introducing CCR Focus: Susan E. Bates, Senior Editor (p. 5255)
• A New Generation of Mouse Models of Cancer for Translational Research: Cory Abate-Shen, Guest Editor (p. 5274)
• The Use of Targeted Mouse Models for Preclinical Testing of Novel Cancer Therapeutics: Kenneth P. Olive and David A. Tuveson (p. 5277)
• Mouse Models of Brain Tumors and Their Applications in Preclinical Trials: Elena I. Fomchenko and Eric C. Holland (p. 5288)
• A Mouse Model System to Genetically Dissect the Molecular Mechanisms Regulating Tumorigenesis:
  Kurt Degenhardt and Eileen White (p. 5296)
• Mouse Modeling in Oncologic Preclinical and Translational Research: Brett S. Carver and Pier P. Pandolfi (p. 5305)
• Using Genetically Engineered Mouse Models of Cancer to Aid Drug Development: An Industry Perspective: Mallika Singh and Leisa Johnson (p. 5312)

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MMP Genes Associated with Decreased Survival in Lung Cancer

Heist et al.
Page 5448

The matrix metalloproteinases (MMP) are a family of enzymes that can degrade extracellular matrix and facilitate invasion through the basement membrane. Heist et al. investigated whether, due to their potential role in aggressiveness and spread of cancer, polymorphisms in MMP genes were associated with survival outcomes in lung cancer. Among 382 Stage I non–small cell lung cancer patients treated with surgical resection, carrying the variant G allele of the MMP-12 1082A/G polymorphism was associated with decreased survival. These findings show promise in finding molecular markers of prognosis in lung cancer, which may help risk stratify patients and inform treatment decisions in the future.

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Pyrimidine Metabolism Differs Between Races

Mattison et al.
Page 5491

African-American colorectal cancer patients receiving 5-fluorouracil experience increased cytopenias and decreased survival compared with Caucasian patients, suggesting racial differences in pyrimidine metabolism. In this study, Mattison et al. used two methods for assessing pyrimidine catabolism in 149 African-American and 109 Caucasian subjects. African Americans were observed to have significantly lower DPD enzyme activity compared with Caucasians (P = 0.002). Of note, African-American women had the lowest mean DPD activity and highest prevalence of DPD deficiency. These data suggest that African Americans, particularly African-American women, may be at risk for 5-fluorouracil toxicity resulting from reduced pyrimidine catabolism.

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High-Throughput Screen Identifies Novel Anticancer Drugs

Yip et al.
Page 5557

Yip et al. report a cell-based, phenotype-driven high throughput screen (HTS) for the identification of head and neck cancer therapeutics. This HTS successfully identified known anticancer agents such as paclitaxel, from the LOPAC1280 and Prestwick compound libraries. Several novel compounds, such as benzethonium chloride, were also identified via this HTS. Further characterization of benzethonium chloride confirmed its significant anticancer specificity, mediated primarily through an apoptotic mechanism, with efficacy both in vitro and in vivo. Such a HTS approach could therefore be used for large-scale compound screening, facilitating the identification and characterization of novel anticancer therapeutics.

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