![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication December 17, 2004.
Revised March 3, 2005.
Accepted for publication March 31, 2005.
The seminal epidemiological observation that nonsteroidal anti-inflammatory drugs (NSAIDs) prevent colon and possibly other cancers has spurred novel approaches to cancer prevention. The known inhibitory effect of NSAIDs on the eicosanoid pathway prompted studies focusing on cyclooxygenase (COX) and its products. The increased PGE2 levels and the overexpression of COX-2 in colon and many other cancers provided the rationale for clinical trials with COX-2 inhibitors for cancer prevention or treatment. Their efficacy in the prevention of sporadic colon and other cancers remains unknown; one COX-2 inhibitor has been withdrawn due to side effects and there are concerns about whether this effect is class-specific. There is evidence to suggest that COX-2 may not be the only or the ideal eicosanoid pathway target for cancer prevention. Six sets of observations support this notion: the relatively late induction of COX-2 during carcinogenesis; the finding that NSAIDs may not require inhibition of COX-2 for their effect; the modest effect of coxibs in cancer prevention; that currently available coxibs have multiple non-COX-2 effects which may account for at least some of their efficacy; the possibility that concurrent inhibition of COX-2 in non-neoplastic cells may be harmful; and the possibility that COX-2 inhibition may modulate alternative eicosanoid pathways in a way promoting carcinogenesis. Given the limitations of COX-2 specific inhibitors and the biological evidence mentioned above, we suggest that targets other than COX-2 should be pursued as alternative or complementary approaches to cancer prevention.
Key words:
COX-1, COX-2, COX-2 independent targets, Chemoprevention, Colon cancer, NSAIDs
This article has been cited by other articles:
|
|
 |
|
  Y. Bren-Mattison, A. M. Meyer, V. Van Putten, H. Li, K. Kuhn, R. Stearman, M. Weiser-Evans, R. A. Winn, L. E. Heasley, and R. A. Nemenoff Antitumorigenic Effects of Peroxisome Proliferator-Activated Receptor-{gamma} in Non-Small-Cell Lung Cancer Cells Are Mediated by Suppression of Cyclooxygenase-2 via Inhibition of Nuclear Factor-{kappa}B Mol. Pharmacol., March 1, 2008; 73(3): 709 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhao, M. Goswami, N. Pokhriyal, H. Ma, H. Du, J. Yao, T. A. Victor, K. Polyak, C. D. Sturgis, H. Band, et al. Cyclooxygenase-2 Expression during Immortalization and Breast Cancer Progression Cancer Res., January 15, 2008; 68(2): 467 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. McIlhatton, J. Tyler, S. Burkholder, J. Ruschoff, B. Rigas, L. Kopelovich, and R. Fishel Nitric Oxide Donating Aspirin Derivatives Suppress Microsatellite Instability in Mismatch Repair Deficient and Hereditary Nonpolyposis Colorectal Cancer Cells Cancer Res., November 15, 2007; 67(22): 10966 - 10975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Gillespie, M. W. Moody, F.-S. Lee, L. J. Poole, J. D. Hornig, D. Lathers, M. R. Young, and T. A. Day Head and Neck Cancer Recurrence and Mortality in Nonselective Cyclooxygenase Inhibitor Users Arch Otolaryngol Head Neck Surg, January 1, 2007; 133(1): 28 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ding, R. Feng, S. Y. Wang, L. Bowman, Y. Lu, Y. Qian, V. Castranova, B.-H. Jiang, and X. Shi Cyanidin-3-glucoside, a Natural Product Derived from Blackberry, Exhibits Chemopreventive and Chemotherapeutic Activity J. Biol. Chem., June 23, 2006; 281(25): 17359 - 17368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-S. Liu, L.-F. Liu, C.-J. Lin, J.-C. Tseng, M.-J. Chuang, H.-C. Lam, J.-K. Lee, L.-C. Yang, J. H. Y. Chan, S.-L. Howng, et al. Gene Transfer of Pro-opiomelanocortin Prohormone Suppressed the Growth and Metastasis of Melanoma: Involvement of {alpha}-Melanocyte-Stimulating Hormone-Mediated Inhibition of the Nuclear Factor {kappa}B/Cyclooxygenase-2 Pathway Mol. Pharmacol., February 1, 2006; 69(2): 440 - 451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. G. Knight, D. F. Kraemer, and E. A. Neuwelt Ototoxicity in Children Receiving Platinum Chemotherapy: Underestimating a Commonly Occurring Toxicity That May Influence Academic and Social Development J. Clin. Oncol., December 1, 2005; 23(34): 8588 - 8596. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
