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Novel Therapeutics: NSAIDs, Derivatives, and Phosphodiesterases

  • Molecular Biology (S Anant, Section Editor)
  • Published:
Current Colorectal Cancer Reports

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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Acknowledgement

G.A. Piazza has received financial support through a grant from the National Institutes of Health.

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No potential conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Department of Biology, Chemistry and Mathematics, University of Montevallo, Station 6480, Montevallo, AL, 35115, USA

    Heather N. Tinsley

  2. Drug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue Suite 3029, Mobile, AL, 36604, USA

    Gary A. Piazza

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  1. Heather N. Tinsley
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  2. Gary A. Piazza
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Correspondence to Heather N. Tinsley.

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Tinsley, H.N., Piazza, G.A. Novel Therapeutics: NSAIDs, Derivatives, and Phosphodiesterases. Curr Colorectal Cancer Rep 8, 325–330 (2012). https://doi.org/10.1007/s11888-012-0142-5

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