Abstract
In addition to the key role of thrombin in blood coagulation, this multifunctional serine protease activates platelets and regulates the behavior of other cells through G-protein coupled protease activated receptors (PARs). PAR-1 is the principal thrombin-activated receptor involved in platelet aggregation and in endothelial and tumor cell proliferation. PAR-1 is overexpressed in invasive and metastatic tumors and the expression levels directly correlate with the degree of invasiveness of the cancer. In an attempt to give some insight into the perspectives of targeting PAR-1 in cancer and angiogenesis, this review provides an overview on the thrombin/PAR-1 interaction, receptor activation, signaling, desensitization and dysregulation mechanisms in relation to these diseases. A central aspect of this review is that directed to summarize the approaches that have been followed to the search of PAR-1 antagonists, illustrating with some significant examples. Attention is called to the scarce data concerning the effects of these antagonists on anticancer assay models.
Keywords: Cancer, Angiogenesis, Protease-Activated Receptors, Thrombin-Activated Receptors, PAR-1, PAR-1 Agonists and Antagonists
Current Medicinal Chemistry
Title: Thrombin-Activated Receptors: Promising Targets for Cancer Therapy?
Volume: 17 Issue: 2
Author(s): M. T. Garcia-Lopez, M. Gutierrez-Rodriguez and R. Herranz
Affiliation:
Keywords: Cancer, Angiogenesis, Protease-Activated Receptors, Thrombin-Activated Receptors, PAR-1, PAR-1 Agonists and Antagonists
Abstract: In addition to the key role of thrombin in blood coagulation, this multifunctional serine protease activates platelets and regulates the behavior of other cells through G-protein coupled protease activated receptors (PARs). PAR-1 is the principal thrombin-activated receptor involved in platelet aggregation and in endothelial and tumor cell proliferation. PAR-1 is overexpressed in invasive and metastatic tumors and the expression levels directly correlate with the degree of invasiveness of the cancer. In an attempt to give some insight into the perspectives of targeting PAR-1 in cancer and angiogenesis, this review provides an overview on the thrombin/PAR-1 interaction, receptor activation, signaling, desensitization and dysregulation mechanisms in relation to these diseases. A central aspect of this review is that directed to summarize the approaches that have been followed to the search of PAR-1 antagonists, illustrating with some significant examples. Attention is called to the scarce data concerning the effects of these antagonists on anticancer assay models.
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Cite this article as:
Garcia-Lopez T. M., Gutierrez-Rodriguez M. and Herranz R., Thrombin-Activated Receptors: Promising Targets for Cancer Therapy?, Current Medicinal Chemistry 2010; 17 (2) . https://dx.doi.org/10.2174/092986710790112639
DOI https://dx.doi.org/10.2174/092986710790112639 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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