Approach to angiogenesis inhibition based on cyclooxygenase-2
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Updated: Oct 3, 2026
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Published on: June 30, 2023
1Pharmacia Corporation, St. Louis, Missouri 63167, USA.
Abstract:
Two cyclooxygenase (COX) isoforms have been identified: COX-1 and COX-2. COX-1 is the constitutively expressed form of the enzyme and is ubiquitous in its distribution. COX-2 is inducible and is present in inflammatory foci, tumors, and neovasculature. Expression of COX-2 appears to be important in tumor promotion, growth, and metastasis. It is up-regulated in a variety of premalignant disorders and malignancies. COX inhibitors have a major role in the treatment of inflammation and pain. Epidemiologic evidence in patients who take nonsteroidal anti-inflammatory drugs links COX inhibition with decreases in malignant esophageal, stomach, colon, lung, and breast tumors. Nonselective COX inhibitors have demonstrated efficacy in control of familial adenomatous polyposis, a disorder associated with the development of thousands of benign intestinal polyps. The selective COX-2 inhibitor celecoxib (Celebrex, Pharmacia) has been shown to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis as an adjunct to usual care. Celecoxib has recently been approved for this indication and offers the potential for equivalent or greater efficacy than that seen with nonselective COX inhibitors but without the gastrointestinal mucosal toxicity and the inhibition of platelet function associated with those agents. Angiogenesis is a feature of both benign and malignant disease. Because COX-2 is up-regulated in the neovasculature of the rheumatoid pannus and in malignant tumors and their surrounding stroma, selective COX-2 inhibitors may be able to modify the progression of these disorders through the control of angiogenesis.
Insights
Cyclooxygenase-2 (COX-2) inhibitors show promise in cancer prevention and treatment by targeting tumor growth and angiogenesis. Selective COX-2 inhibitors, like celecoxib, offer potential benefits over nonselective drugs with fewer side effects.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Two cyclooxygenase (COX) isoforms, COX-1 and COX-2, exist. COX-1 is constitutive, while COX-2 is inducible and found in inflammatory sites, tumors, and neovasculature.
- COX-2 expression is implicated in tumor promotion, growth, and metastasis, and is upregulated in various cancers.
- COX inhibitors are crucial for managing inflammation and pain, with epidemiological data linking them to reduced risks of several cancers.
Purpose of the Study:
- To explore the role of COX-2 in tumor progression and angiogenesis.
- To evaluate the efficacy and safety of selective COX-2 inhibitors in cancer and related conditions.
Main Methods:
- Review of existing epidemiological and clinical data on COX inhibitors in cancer and inflammation.
- Analysis of the mechanism of action of selective COX-2 inhibitors, focusing on angiogenesis.
- Examination of clinical trial results for celecoxib in familial adenomatous polyposis.
Main Results:
- Epidemiological studies link nonselective COX inhibitors to reduced incidence of esophageal, stomach, colon, lung, and breast tumors.
- Nonselective COX inhibitors are effective in managing familial adenomatous polyposis.
- The selective COX-2 inhibitor celecoxib reduces colorectal polyps in familial adenomatous polyposis and may offer improved safety profiles regarding gastrointestinal and platelet effects.
Conclusions:
- COX-2 plays a significant role in tumor development and progression.
- Selective COX-2 inhibitors, such as celecoxib, demonstrate potential in cancer chemoprevention and treatment, possibly by inhibiting angiogenesis.
- Celecoxib's approval for familial adenomatous polyposis marks a step towards targeted therapies with potentially reduced side effects.
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