The Role of Prostaglandins as Major Inflammatory Mediators in Colorectal Cancer

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality, with inflammation playing a pivotal role in its pathogenesis. Chronic inflammation in the intestine significantly increases the risk of CRC development. Main compounds participating in the inflammatory process are prostaglandins; bioactive lipids derived from arachidonic acid metabolism via the cyclooxygenase (COX) pathway. While it is well known that prostaglandin E₂ (PGE₂) promotes CRC tumorigenesis, other prostaglandins, such as PGD₂, PGF_2α, and prostacyclin (PGI₂), remain relatively underexplored. These prostaglandins may exert distinct or opposing effects on CRC development, but the current understanding of their functions is limited. Additionally, the impact of prostaglandins on immune regulation and the tumor microenvironment, is far from being fully understood. Addressing these knowledge gaps is crucial for identifying novel therapeutic targets and optimizing chemoprevention strategies. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of CRC, largely by inhibiting prostaglandin producing enzymes. However, their use is limited due to their gastrointestinal and cardiovascular side effects. Therefore, understanding the intricate role of inflammation and prostaglandin signaling in CRC is critical to develop safer and more effective chemopreventive approaches. This review summarizes the current knowledge of prostaglandins, linking inflammation and CRC. It further addresses the potential of targeting prostaglandin pathways for chemoprevention. Furthermore, we discuss emerging pharmacological targets that modulate prostaglandin production, signaling or degradation, offering promise for preventing CRC development.