Current Colorectal Cancer Reports

, Volume 8, Issue 4, pp 325–330 | Cite as

Novel Therapeutics: NSAIDs, Derivatives, and Phosphodiesterases

Molecular Biology (S Anant, Section Editor)


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.


Sulindac Colon cancer Nonsteroidal anti-inflammatory drug Cyclic guanosine monophosphate Phosphodiesterase 



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


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


Papers of particular interest, published recently, have been highlighted as follows: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of BiologyChemistry and Mathematics, University of MontevalloMontevalloUSA
  2. 2.Drug Discovery Research CenterMitchell Cancer Institute, University of South AlabamaMobileUSA

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