Endothelin receptors as novel targets in tumor therapy

被引：90

作者：

Bagnato A. ^{[1
]}

Natali P.G. ^{[2
]}

机构：

[1] Molec. Pathology/Ultrastructure Lab., Regina Elena Cancer Institute, 00158 Rome

[2] Department of Immunology Pathology, Regina Elena Cancer Institute, 00158 Rome

来源：

Journal of Translational Medicine | / 2卷 / 1期

关键词：

Vascular Endothelial Growth Factor; Focal Adhesion Kinase; ETBR; Vascular Endothelial Growth Factor Production; Epidermal Growth Factor Receptor Transactivation;

D O I：

10.1186/1479-5876-2-16

中图分类号：

学科分类号：

摘要：

The endotelin (ET) axis, that includes ET-1, ET-2, ET-3, and the ET receptors, ETA and ETB, plays an important physiological role, as modulator of vasomotor tone, tissue differentiation and development, cell proliferation, and hormone production. Recently, investigations into the role of the ET axis in mitogenesis, apoptosis inhibition, invasiveness, angiogenesis and bone remodeling have provided evidence of the importance of the ET-1 axis in cancer. Data suggest that ET-1 participates in the growth and progression of a variety of tumors such as prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast carcinoma, Kaposi's sarcoma, brain tumors, melanoma, and bone metastases. ET-1 receptor antagonists beside providing ideal tools for dissecting the ET axis at molecular level have demonstrated their potential in developing novel therapeutic opportunity. The major relevance of ETA receptor in tumor development has led to an extensive search of highly selective antagonists. Atrasentan, one of such antagonists, is orally bioavailable, has suitable pharmacokinetic and toxicity profiles for clinical use. Preliminary data from clinical trials investigating atrasentan in patients with prostate cancer are encouraging. This large body of evidence demonstrates the antitumor activity of endothelin receptor antagonists and provides a rationale for the clinical evaluation of these molecules alone and in combination with cytotoxic drugs or molecular inhibitors leading to a new generation of anticancer therapies targeting endothelin receptors. © 2004 Bagnato and Natali; licensee BioMed Central Ltd.

引用

页数：9

共 58 条

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