Identification of biomarkers for tumor endothelial cell proliferation through gene expression profiling.

Abstract:

: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.

journal_name

Mol Cancer Ther

authors

Hardwick JS,Yang Y,Zhang C,Shi B,McFall R,Koury EJ,Hill SL,Dai H,Wasserman R,Phillips RL,Weinstein EJ,Kohl NE,Severino ME,Lamb JR,Sepp-Lorenzino L

doi

10.1158/1535-7163.MCT-04-0209

keywords:

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

413-25

issue

3

eissn

1535-7163

issn

1538-8514

pii

4/3/413

journal_volume

4

pub_type

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