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Endothelins as a Potential Target for Anticancer Therapy

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Author(s): Deimante Tamkus | Anas Al-Janadi | Gregory Fink | Ganapathy Krishnan | Nikolay V. Dimitrov

Journal: Journal of Cancer Molecules
ISSN 1816-0735

Volume: 4;
Issue: 6;
Start page: 163;
Date: 2009;
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Keywords: endothelin | angiogenesis | apoptosis | atrasentan | HIF-1alpha

ABSTRACT
The endothelin (ET) system consists of three small peptides (ET-1, ET-2, ET-3) and two ET receptors (ETA and ETB). ETs play key physiologic roles in normal tissue, acting as modulators of vasomotor tone, tissue differentiation, cell proliferation, and hormone production. Besides their physiologic roles, endothelins are implicated in pathologic conditions, such as vascular diseases and cancer. ET system is differentially expressed in invasive cancer compared to precancerous lesions and their normal tissue counterparts. In tumors, ETs exhibit antiapoptotic and angiogenic activities which facilitate malignant growth. Increased ET-1 production and ETA receptor density keeps tumor vessels in vasoconstrictive state, leading to decreased perfusion, hypoxia and resistance to radiotherapy and chemotherapy. In this article, the potential of ETs as a target for anticancer therapy and novel therapeutic strategies are discussed.
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