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Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
The αvβ3 integrin is preferentially expressed on developing and activated endothelial cells, but not quiescent mature vasculature, and is thus considered the most important integrin for angiogenesis. Its primary ligand is vitronectin, but it also binds fibrinogen, fibronectin, and TSP, and associates in cis with MMP2, PDGF, insulin, and VEGFR2. Etaracizumab specifically blocks the binding of vitronectin and other ligands to the αvβ3 integrin and can cause inhibition of angiogenesis. However, blocking this integrin will at least have dose-dependent effects, and so it should be used with caution (the four different scenarios were discussed in relation to αvβ3 integrin inhibition in the earlier section on the introduction to integrins).
How not to discover a drug - integrins
Published in Expert Opinion on Drug Discovery, 2021
Another integrin that showed promise in cancer was α5β1. Volociximab is an α5β1 inhibitor [120] that showed the ability to inhibit angiogenesis [121]. It was tested clinically against ovarian cancer, however, it failed to show any benefit in a PII trial [122].Intetumumab is an anti-αV antibody that was tested in a PII study for melanoma. While there was no evidence of any drug-related toxicity there was no evidence of any benefit either [123]. Etaracizumab is a specific anti-αVβ3 antibody [124] that has been tested in a PII melanoma study. There was little evidence for a significant benefit over standard-of-care [125]. Another anti-αV antibody is abituzumab, which has been shown to prevent prostate cancer cell attachment and invasion [126]. It has shown evidence of some benefit in a PII study in prostate cancer [127].