Inflammatory mediators and NSAID effects

When tissues are injured or infected, the enzyme cyclooxygenase-2 converts arachidonic acid into prostaglandins—lipid signaling molecules that drive inflammation, pain, and fever, but that also influence immune regulation and tumor growth. Non-steroidal anti-inflammatory drugs (NSAIDs) and the more selective COX-2 inhibitors such as celecoxib block this pathway, which is why they relieve inflammation and why epidemiological evidence has linked their regular use to reduced rates of colorectal and other cancers. That chemopreventive potential, however, sits uncomfortably alongside evidence that prolonged COX-2 inhibition raises cardiovascular risk—a tradeoff that derailed several large prevention trials in the early 2000s and removed rofecoxib from the market. Current research is working to understand precisely how prostaglandin E2 suppresses anti-tumor immunity and whether it is possible to target specific prostaglandin receptors or downstream signaling steps to capture the cancer-protective benefits without the cardiovascular liability.

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Keywords

Cyclooxygenase-2 InhibitorsInflammationCancerProstaglandinsNSAIDsCardiovascular Risk