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Cyclooxygenase 2: a molecular target for cancer prevention and treatment
Kotha Subbaramaiah1, Andrew J Dannenberg
1Weill Medical College of Cornell University, Dept of Medicine, New York, NY 10021, USA.
Abstract:
Cyclooxygenase2 (COX-2), an inducible prostaglandin G/H synthase, is overexpressed in several human cancers. Here, the potential utility of selective COX-2 inhibitors in the prevention and treatment of cancer is considered. The mechanisms by which COX-2 levels increase in cancers, key data that indicate a causal link between increased COX-2 activity and tumorigenesis, and possible mechanisms of action of COX-2 are discussed. In a proof-of-principle clinical trial, treatment with the selective COX-2 inhibitor celecoxib reduced the number of colorectal polyps in patients with familial adenomatous polyposis. Selective COX-2 inhibitors appear to be sufficiently safe to permit large-scale clinical testing and numerous clinical trials are currently under way to determine whether selective inhibitors of COX-2 are effective in the prevention and treatment of cancer.
Insights
Selective cyclooxygenase-2 (COX-2) inhibitors show promise for cancer prevention and treatment. Clinical trials indicate their safety and potential efficacy, particularly in reducing colorectal polyps.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Cyclooxygenase-2 (COX-2) is overexpressed in various human cancers.
- Increased COX-2 activity is linked to tumorigenesis.
- Understanding COX-2's role is crucial for cancer therapy.
Purpose of the Study:
- To evaluate the potential of selective COX-2 inhibitors in cancer prevention and treatment.
- To discuss the mechanisms of COX-2 overexpression and action in cancer.
- To review clinical evidence supporting COX-2 inhibitor utility.
Main Methods:
- Review of mechanisms of COX-2 upregulation in cancer.
- Analysis of data linking COX-2 activity to tumorigenesis.
- Discussion of potential COX-2 inhibitor mechanisms of action.
- Consideration of a proof-of-principle clinical trial data.
Main Results:
- A clinical trial demonstrated that celecoxib, a selective COX-2 inhibitor, reduced colorectal polyps in familial adenomatous polyposis patients.
- Selective COX-2 inhibitors appear to have an acceptable safety profile for extensive clinical evaluation.
Conclusions:
- Selective COX-2 inhibitors represent a potential strategy for cancer prevention and treatment.
- Further large-scale clinical trials are warranted to confirm efficacy in diverse cancer types.
- COX-2 inhibition warrants continued investigation as a cancer therapeutic avenue.