Journal de la science cellulaire et de la thérapie
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Pharmacological and Clinical Importance of Integrin Antagonists in Treatment of Cancer

Sasidhar Reddy Eda, Devarai Santhosh Kumar and Rajeswari Jinka

Integrins are heterodimeric molecules that are composed of 18 α-subunits and 8 β-subunits. They exist in 24 distinctive shapes based on combination of these sub-units and are mainly responsible for the adhesion of extracellular matrix (ECM) and immunoglobulin family molecules. Integrins mediate adhesion of epithelial cells to the basement membrane and also help in the migration, proliferation and survival of tumor cells. Studies also reveal that certain integrins act as markers for tumor cells and they also assist in both tumor progression and apoptosis. Studies reveal that unligated integrins in association with caspase 8 result in inhibition of ECM adhesion might result and integrin mediated death (IMD) on the other hand integrins in association with oncogenes or receptor tyrosine kinases can result in enhanced tumorigenesis. Among several types of integrins, αvβ3 and α5β1 have gained importance in anti-angiogenesis studies. Hence the role of antiangiogenesis antagonists has come into light. These include a variety of monoclonal antibodies and peptides. Each one of them has their own mechanism of action and antiangiogenesis activity. Current review aims at studying the phase 1 and 2 trails of these antagonists for anti-angiogenic function.