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Current Colorectal Cancer Reports

Erschienen in:

01.12.2012 | Molecular Biology (S Anant, Section Editor)

Novel Therapeutics: NSAIDs, Derivatives, and Phosphodiesterases

verfasst von: Heather N. Tinsley, Gary A. Piazza

Erschienen in: Current Colorectal Cancer Reports | Ausgabe 4/2012

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Abstract

The chemopreventive efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) for colorectal cancer has been well documented. However, long-term use of NSAIDs is precluded owing to potentially fatal toxicities associated with their mechanism of action involving cyclooxygenase (COX) inhibition. But studies have shown that their anticancer activity may be due, in part, to an off-target effect. Cyclic guanosine monophosphate (cGMP) phosphodiesterases (PDEs), which are responsible for negative regulation of cGMP signaling, are an attractive COX-independent target. cGMP signaling is aberrantly suppressed in cancer cells and its activation appears to be sufficient to inhibit tumor cell growth. Chemically modifying sulindac has produced a series of new derivatives that lack COX-inhibitory activity but have improved cGMP PDE inhibitory activity. This approach is proving to be a promising strategy for the discovery of improved agents for the prevention and/or treatment of colorectal cancer.

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Titel: Novel Therapeutics: NSAIDs, Derivatives, and Phosphodiesterases
verfasst von: Heather N. Tinsley
Gary A. Piazza
Publikationsdatum: 01.12.2012
Verlag: Current Science Inc.
Erschienen in: Current Colorectal Cancer Reports / Ausgabe 4/2012
Print ISSN: 1556-3790
Elektronische ISSN: 1556-3804
DOI: https://doi.org/10.1007/s11888-012-0142-5

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