Improvement strategies for molecular targeting: Cyclooxygenase-2 inhibitors as radiosensitizers for non-small cell lung cancer.

Cyclooxygenase-2 (COX-2) is an enzyme involved in prostaglandin production in pathologic states such as inflammatory processes and cancer. The enzyme is often overexpressed in premalignant lesions and various cancers, including cancer of the lung. Inhibition of this enzyme with selective COX-2 inhibitors was found to enhance tumor response to radiation in preclinical studies, suggesting that these agents can improve the response of various cancers to radiotherapy. On the basis of these preclinical findings, we initiated clinical trials of the combination of celecoxib, a selective COX-2 inhibitor, with radiotherapy in patients with lung cancer. Here we discuss the rationale for using selective COX-2 inhibitors and describe current clinical protocols and the initial findings.