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New NSAID Targets and Derivatives for Colorectal Cancer Chemoprevention

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Prospects for Chemoprevention of Colorectal Neoplasia

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 191))

Abstract

Clinical and preclinical studies provide strong evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) can prevent numerous types of cancers, especially colorectal cancer. Unfortunately, the depletion of physiologically important prostaglandins due to cyclooxygenase (COX) inhibition results in potentially fatal toxicities that preclude the long-term use of NSAIDs for cancer chemoprevention. While studies have shown an involvement of COX-2 in colorectal tumorigenesis, other studies suggest that a COX-independent target may be at least partially responsible for the antineoplastic activity of NSAIDs. For example, certain NSAID derivatives have been identified that do not inhibit COX-2 but have demonstrated efficacy to suppress carcinogenesis with potential for reduced toxicity. A number of alternative targets have also been reported to account for the tumor cell growth inhibitory activity of NSAIDs, including the inhibition of cyclic guanosine monophosphate phosphodiesterases (cGMP PDEs), generation of reactive oxygen species (ROS), the suppression of the apoptosis inhibitor protein, survivin, and others. Here, we review several promising mechanisms that are being targeted to develop safer and more efficacious NSAID derivatives for colon cancer chemoprevention.

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Acknowledgments

Funding provided by NIH grants R01 CA131378 and R01 CA148817 and a UAB Breast Cancer SPORE grant.

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Authors and Affiliations

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

    Heather N. Tinsley

  2. Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, USA

    William E. Grizzle

  3. Faculty of Pharmacy and Biotechnology, German University of Cairo, Cairo, Egypt

    Ashraf Abadi

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

    Adam Keeton, Bing Zhu, Yaguang Xi & Gary A. Piazza

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  1. Heather N. Tinsley
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  2. William E. Grizzle
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  3. Ashraf Abadi
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  4. Adam Keeton
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  5. Bing Zhu
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  6. Yaguang Xi
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  7. Gary A. Piazza
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Correspondence to Gary A. Piazza .

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Editors and Affiliations

  1. Massachusetts General Hospital, Gastrointestinal Unit, Harvard Medical School, Fruit Street 55, Boston, 02114, Massachusetts, USA

    Andrew T. Chan

  2. BSP-GD-GMA-CVRM, Berlin, S101, 09, 140, Bayer Schering Pharma AG, Müllerstraße 178, Berlin, 13351, Germany

    Elmar Detering

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Tinsley, H.N. et al. (2013). New NSAID Targets and Derivatives for Colorectal Cancer Chemoprevention. In: Chan, A., Detering, E. (eds) Prospects for Chemoprevention of Colorectal Neoplasia. Recent Results in Cancer Research, vol 191. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30331-9_6

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