Multiple lines of evidence suggest that cyclooxygenase-2 (COX-2) upregulation is an early event in the development of non-small-cell lung cancer. Preclinical data indicate tumors with upregulation of COX-2 synthesize high levels of prostaglandin E₂ (PGE₂), which in turn are associated with increased production of proangiogenic factors and enhanced metastatic potential. These findings indicate that an increase in COX-2 expression may play a significant role in the development and growth of lung cancers and possibly with the acquisition of an invasive and metastatic phenotype. Consequently, inhibitors of COX-2 are being studied for their chemopreventative and therapeutic effects in individuals at high risk for lung cancer and patients with established cancers.