Combined chemotherapy with cyclooxygenase-2 (COX-2) inhibitors in treating human cancers: Recent advancement

Chemotherapy with a single chemotherapeutic agent or a combined chemotherapeutic regimen is the clinically standardized treatment for almost all human cancers. Upregulated expression of cyclooxygenase (COX)-2, also known as prostaglandin-endoperoxide synthase (PTGS), is associated with human carcinogenesis and cancer progression and COX-2 inhibitors show antitumor activity in different human cancers. Thus, a combination of chemotherapeutic agents with COX-2 inhibitors has been shown to improve therapeutic effects on human cancers. This review discusses and summarizes recent advances in cancer control and treatment using various antineoplastic drugs combined with COX-2 inhibitors. These combinations showed synergistic antitumor effects. At the gene level, COX-2 inhibitors can reduce inflammatory factors thereby regulating macrophage recruitment for activating the antitumor immune microenvironment; downregulating vascular endothelial growth factor (VEGF) to inhibit tumor angiogenesis; and inhibiting the PI3K/Akt signaling pathway to induce tumor cell apoptosis. In addition, such a combination can reduce toxicity and chemoresistance and enhance radiosensitivity, although COX-2 inhibitors-related cardiotoxicity may potentially affect its use. Further in-depth investigation of these drug combinations is needed to maximize antitumor efficacy and minimize the side effects.