This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hardwick, J. S. Articles by Sepp-Lorenzino, L. Search for Related Content PubMed PubMed Citation Articles by Hardwick, J. S. Articles by Sepp-Lorenzino, L.

¹ Merck Research Laboratories, West Point, Pennsylvania and ² Rosetta Inpharmatics LLC, Seattle, Washington

Requests for reprints: James S. Hardwick, Merck & Co., Inc., 770 Sumneytown Pike, WP26-462, West Point, PA 19486. Phone: 215-652-4075; Fax: 215-993-3398. E-mail: james_hardwick{at}merck.com

Extensive efforts are under way to identify antiangiogenic therapies for the treatment of human cancers. Many proposed therapeutics target vascular endothelial growth factor (VEGF) or the kinase insert domain receptor (KDR/VEGF receptor-2/FLK-1), the mitogenic VEGF receptor tyrosine kinase expressed by endothelial cells. Inhibition of KDR catalytic activity blocks tumor neoangiogenesis, reduces vascular permeability, and, in animal models, inhibits tumor growth and metastasis. Using a gene expression profiling strategy in rat tumor models, we identified a set of six genes that are selectively overexpressed in tumor endothelial cells relative to tumor cells and whose pattern of expression correlates with the rate of tumor endothelial cell proliferation. In addition to being potential targets for antiangiogenesis tumor therapy, the expression patterns of these genes or their protein products may aid the development of pharmacodynamic assays for small molecule inhibitors of the KDR kinase in human tumors.

Key Words: angiogenesis • KDR • VEGF • endothelial cell • biomarkers • gene expression profiling

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

³ http://www.ncbi.nlm.nih.gov/geo/

⁴ http://docs.appliedbiosystems.com/pebiodocs/04333458.pdf

⁵ http://docs.appliedbiosystems.com/pebiodocs/04303859.pdf

⁶ Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

⁷ J. Antanavage, R. McFall, and K. Thomas, personal communication.

⁸ B. Shi et al., manuscript in preparation.

⁹ K. Thomas, J. Antanavage, and R. McFall, personal communication.

Received 8/17/04; revised 12/16/04; accepted 1/13/05.