Integrin alpha(v)beta(3)-Targeted Cancer Therapy.

Drug Development Research
Zhaofei LiuXiaoyuan Chen

Abstract

Anti-angiogenesis is a promising strategy for the treatment of cancer. Integrins, consisting of two noncovalently bound transmembrane alpha and beta subunits, are an important molecular family involved in tumor angiogenesis. The blockade of integrin signaling has been demonstrated to be efficient to inhibit tumor growth, angiogenesis, and metastasis. Among all the integrins, alpha(v)beta(3) seems to be the most important one during tumor angiogenesis. The inhibition of integrin alpha(v)beta(3) signaling with antibodies, peptides, peptidomimetics, and other antagonists has great potential in the treatment of cancer. In addition, integrin alpha(v)beta(3) is highly expressed on activated endothelial cells, new-born vessels as well as some tumor cells, but is not present in resting endothelial cells and most normal organ systems, making it a suitable target for anti-angiogenic therapy. In this article we will review the role of integrin alpha(v)beta(3) in angiogenesis, present recent progress in the use of integrin alpha(v)beta(3) antagonists and integrin-targeted delivery systems as potential cancer therapeutics, and discuss future perspectives.

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