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

Abstract

Cyclooxygenase-2 (COX-2) inhibitors are widely used as antiinflammatory 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.

Keywords

COX-2 inhibitor / Tumor therapy / Nanomedicine / Immunotherapy / Drug delivery

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