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The role of COX-2 in intestinal inflammation and colorectal cancer

Abstract

Colorectal cancer (CRC) is a heterogeneous disease, including at least three major forms: hereditary, sporadic and colitis-associated CRC. A large body of evidence indicates that genetic mutations, epigenetic changes, chronic inflammation, diet and lifestyle are the risk factors for CRC. As elevated cyclooxygenase-2 (COX-2) expression was found in most CRC tissue and is associated with worse survival among CRC patients, investigators have sought to evaluate the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXIBs) on CRC. The epidemiological studies, clinical trials and animal experiments indicate that NSAIDs are among the most promising chemopreventive agents for this disease. NSAIDs exert their anti-inflammatory and antitumor effects primarily by reducing prostaglandin production by inhibition of COX-2 activity. In this review, we highlight breakthroughs in our understanding of the roles of COX-2 in CRC and inflammatory bowel disease. These recent data provide a rationale for re-evaluating COX-2 as both the prognostic and the predictive marker in a wide variety of malignancies and for renewing the interest in evaluating relative benefits and risk of COXIBs in appropriately selected patients for cancer prevention and treatment.

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Acknowledgements

This work was supported, in part, from the National Institutes of Health Grants RO1DK 62112, P01-CA-77839, R37-DK47297 and P30 DK-58404 (RND). RND (R37-DK47297) is recipient of an NIH MERIT award. We also thank the National Colorectal Cancer Research Alliance (NCCRA) for generous support (RND).

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Wang, D., DuBois, R. The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene 29, 781–788 (2010). https://doi.org/10.1038/onc.2009.421

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