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Cyclooxygenase-2 and Epidermal Growth Factor Receptor: Pharmacologic Targets for Chemoprevention

Andrew J. Dannenberg, Scott M. Lippman, Jason R. Mann, Kotha Subbaramaiah, Raymond N. DuBois

From the Department of Medicine, Weill Medical College of Cornell University, New York, NY; Departments of Clinical Cancer Prevention and Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX; and Departments of Medicine, Cancer Biology, and Cell & Developmental Biology, Vanderbilt University Medical Center and the Vanderbilt-Ingram Cancer Center, Nashville, TN

Address reprint requests to Raymond N. DuBois, MD, PhD, Vanderbilt-Ingram Cancer Center, 691 Preston Research Building, 2300 Pierce Avenue, Nashville, TN 37232-6838; e-mail: raymond.dubois{at}vanderbilt.edu.

Understanding the mechanisms underlying carcinogenesis provides insights that are necessary for the development of therapeutic strategies to prevent cancer. Chemoprevention, the use of drugs or natural substances to inhibit carcinogenesis, is a rapidly evolving aspect of cancer research. Evidence is presented that cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) are potential pharmacologic targets to prevent cancer. In this paper, we review key data implicating a causal relationship between COX-2, EGFR, and carcinogenesis and possible mechanisms of action. We discuss evidence of crosstalk between COX-2 and EGFR in order to strengthen the rationale for combination chemoprevention, and review plans for a clinical trial that will evaluate the concept of combination chemoprevention targeting COX-2 and EGFR.

Supported by the United States Public Health Service Grants RO1-DK-62112, R01-CA82578, R01-89578, PO1-CA77839 and P01-CA106451. A.J.D. is the Henry R. Erle, M.D.-Roberts Family Professor of Medicine. R.N.D. is the Hortense B. Ingram Professor of Molecular Oncology and the recipient of a National Institutes of Health MERIT award (R37-DK47297).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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