A Contemporary Review on the Critical Role of Nonsteroidal Anti-inflammatory Agents in Colorectal Cancer Therapy.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are widely recognized as effective pain relievers and function by inhibiting the cyclooxygenase enzyme (COXs). Moreover, they have been found to participate in various cellular processes through different signaling pathways, such as WNT, MAPK, NF-κB, and PI3K/AKT/mTOR. This makes them potential candidates for chemoprevention of several malignancies, particularly colorectal cancer (CRC). However, the use of NSAIDs in cancer prevention and treatment is a complex issue due to their adverse effects and gastrointestinal toxicity. Therefore, it is crucial to explore combination therapies that can minimize side effects while maximizing synergistic effects with other agents and to evaluate the success rate of such approaches in both pre-clinical and clinical studies. In this review, we aim to provide an overview of the effects of NSAIDs in the prevention and treatment of CRC. We will focus on elucidating the possible mechanisms of action of these drugs, the signaling pathways involved in CRC, and the potential synergistic effects when combined with other therapeutic agents.