Repurposing COX-2 Inhibitors for Cancer Therapy: Advances in Nanomedicine Delivery

doi:10.1007/s40242-026-5309-8

Abstract

Abstract: Cyclooxygenase-2 (COX-2) inhibitors are widely used as anti-inflammatory agents in clinical treatments. Increasing evidence indicates that COX-2 is overexpressed in most tumors, and its downstream metabolites play crucial roles in tumor inititation, growth, and metastasis. Although COX-2 inhibitors do not exert direct cytotoxic effects on cancer cells, they can suppress tumor progression by reducing the production of prostaglandin E₂ (PGE₂). Therefore, COX-2 inhibitors have emerged as promising antitumor adjuvants. However, when combined with conventional antitumor drugs, the clinical application of COX-2 inhibitors is often limited by mismatched physicochemical properties and dose-related adverse effects. Nanotechnology offers effective solutions to these challenges by improving drug delivery efficiency and reducing systemic toxicity. In this review, we summarize the rationale and fundamental mechanisms underline the antitumor effects of COX-2 inhibitors. We further highlight their emerging role as antitumor companions in synergistic immunotherapy, suppression of tumor recurrence after chemotherapy, enhancement of chemotherapy efficacy, amplification of photothermal and photodynamic therapies (PDT/PTT), and facilitation of combination strategies involving ferroptosis.

Key words: COX-2 inhibitor, Tumor therapy, Nanomedicine, Immunotherapy, Drug delivery

XU Henan, ZHANG Ruohao, WANG Daguang, JIANG Yuxin, FENG Jing, ZHANG Hongjie. Repurposing COX-2 Inhibitors for Cancer Therapy: Advances in Nanomedicine Delivery[J]. Chemical Research in Chinese Universities, 2026, 42(2): 557-570.

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