Molecular Biology (S Anant, Section Editor)

Current Colorectal Cancer Reports

, Volume 8, Issue 4, pp 325-330

First online:

Novel Therapeutics: NSAIDs, Derivatives, and Phosphodiesterases

  • Heather N. TinsleyAffiliated withDepartment of Biology, Chemistry and Mathematics, University of Montevallo Email author 
  • , Gary A. PiazzaAffiliated withDrug Discovery Research Center, Mitchell Cancer Institute, University of South Alabama

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access


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