The Importance of Drug Concentration at the Site of Action: Celecoxib and Colon Polyp Prevention as a Case Study.

Abstract

Celecoxib is among the more potent and better clinically studied, nonsteroidal anti-inflammatory drugs (NSAID) for use as a chemoprevention agent for colorectal cancer. Its use is associated with a 40% to 50% response rate for reduction in adenomatous polyps. However, rare serious cardiovascular effects and even death with celecoxib and other NSAIDs make it important to understand why some patients respond and others do not. Celecoxib is a selective inhibitor of COX-2. Its anticancer mechanism has largely been attributed to the inhibition of COX-2. Celecoxib also shows activity to induce apoptosis in cancer cells not expressing COX-2. This includes activity to upregulate 15-lipoxygenase-1 (15-LOX-1) independent of COX-2 and increase the synthesis of 13-S-hydroxyoctadecadienoic acid (13-S-HODE) from linoleic acid (LA) to downregulate PPAR-δ and induce apoptosis in colorectal cancer models. In examining the effect of celecoxib on 15-LOX-1 for reducing adenomatous polyps in patients with familial adenomatous polyposis (FAP), Yang and colleagues point out the potential importance of drug bioavailability in blood, normal, and neoplastic colorectal tissue in patient response. See related article, p. 217.

• Authors: Patricia A Thompson, Jessica A Martinez
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 15 Issue 4 Pg. 205-208 (04 01 2022) ISSN: 1940-6215 [Electronic] United States
• PMID: 35373257 (Publication Type: Editorial, Comment)
• Copyright: ©2022 American Association for Cancer Research.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase Inhibitors
• Sulfonamides
• Celecoxib

Topics

• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Celecoxib (pharmacology, therapeutic use)
• Colon (drug effects)
• Cyclooxygenase Inhibitors (pharmacology)
• Humans
• Sulfonamides (pharmacology, therapeutic use)