Cyclooxygenase-2 selective inhibitors in cancer prevention and therapy: inflammopharmacological basis and translational prospects.

Cyclooxygenase-2 (COX-2) selective inhibitors, originally developed as anti-inflammatory and analgesic agents for musculoskeletal disorders, show improved gastrointestinal safety compared with traditional nonsteroidal anti-inflammatory drugs and have attracted increasing interest for their potential roles in cancer prevention and treatment. Experimental and clinical evidence indicates that blocking the COX-2/prostaglandin pathway can inhibit tumor initiation and progression by modulating chronic inflammation, angiogenesis, apoptosis, tumor immunity and metastatic spread, with particularly strong data in colorectal cancer. At the same time, concerns about cardiovascular toxicity and heterogeneous treatment responses highlight the need for careful patient selection and optimized dosing strategies. This review summarizes the pharmacological characteristics of COX-2 selective inhibitors and current preclinical and clinical evidence for their anticancer activity across different tumor types. We focus on the underlying mechanisms linking COX-2 signaling to tumor biology, resistance to chemotherapy and radiotherapy, and the potential benefits of combining COX-2 inhibitors with cytotoxic drugs, targeted agents or immunotherapy. In addition, we discuss emerging strategies such as biomarker-guided precision use and novel drug delivery systems designed to enhance antitumor efficacy while reducing systemic adverse effects, and we outline key questions that must be addressed before COX-2 selective inhibitors can be more widely and safely integrated into oncology practice.