Epidemiological studies have long suggested that NSAIDs, prototypic inhibitors of cyclooxygenase (COX), can prevent the development of a variety of solid malignancies. An abundance of pre-clinical and early clinical data now also suggest that selective COX-2 inhibitors have a potential role as targeted therapy against existing neoplasms. High-level expression of COX-2 is induced in many tissues by pro-inflammatory cytokines (IL-1, TNF-), growth factors (EGF, PDGF, FGF, TGF-), carcinogens and oncogenes (Ras, Src, HER2, Wnt)[1, 2]. Production of prostaglandins, particularly PGE2, is an important event in carcinogenesis, and indeed the COX-2 pathway has been implicated in the initiation and promotion of a host of malignancies. In fact, COX-2 expression (protein and/or mRNA) has been demonstrated in the majority of human solid neoplasms. As discussed below, the level of COX-2 in a tumor can have prognostic implications.

Pre-clinically, selective COX-2 inhibitors suppress angiogenesis, induce apoptosis, and decrease the incidence of lung metastases from implanted solid tumors. The beneficial effects of selective COX-2 inhibitors appear to be additive or synergistic with therapeutic irradiation, as well as a variety of chemotherapeutic agents. Clinically, treatment with both nonselective and selective COX inhibitors leads to regression of neoplastic lesions, such as duodenal and colonic polyps. A variety of adjuvant and advanced disease clinical