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Strategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists
Sheldrake, Helen M. Patterson, Laurence H.
Sheldrake, Helen M.
Patterson, Laurence H.
Publication Date
2014
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This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, copyright © 2014 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jm5000547
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Abstract
The integrins are a family of 24 heterodimeric transmembrane cell surface receptors. Involvement in cell attachment to the extracellular matrix, motility, and proliferation identifies integrins as therapeutic targets in cancer and associated conditions; thrombosis, angiogenesis and osteoporosis. The most reported strategy for drug development is synthesis of an agent that is highly selective for a single integrin receptor. However, the ability of cancer cells to change their integrin repertoire in response to drug treatment renders this approach vulnerable to the development of resistance and paradoxical promotion of tumor growth. Here, we review progress towards development of antagonists targeting two or more members of the RGD-binding integrins, notably αvβ3, αvβ5, αvβ6, αvβ8, α5β1, and αIIbβ3, as anticancer therapeutics.
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Citation
Sheldrake HM and Patterson LH (2014) Strategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists. Journal of Medicinal Chemistry. 57(15): 6301-6315.
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