Cox-2 and Cancer

Experimental and clinical evidence supports the view that the inducible isoform of cyclooxygenase (COX-2) plays a crucial role in oncogenesis. Findings extrapolated from experimental studies in cultured tumour cells and animal tumour models indicate that COX-2 critically influences all stages of tumour development from tumour initiation to metastatization. Moreover, clinical and epidemiological data indicate that aberrant regulation of cyclooxygenase-2 is associated with adverse clinical outcome in different types of malignancies. COX-2 overexpression in tumour cells results in stimulation of growth, increased cell survival, enhanced tumour cell invasiveness, stimulation of neovascularization, and tumour evasion from the host immune system. Moreover, COX-2 is capable to modify the extracellular milieu and to create a pro-inflammatory environment contributing to tumour initiation and tumour growth. The initial enthusiasm generated by the discovery of COX-2 selective inhibitors and their use for cancer prevention and therapy has been tempered by the severe cardiovascular adverse side effects associated with their long-term use. Therefore, our ability to efficiently target the oncogenic effects of COX-2 for therapeutic and preventive purposes strictly depends on a better understanding of the molecular mechanisms of its spatial and temporal regulation in tumour cells. The emerging role of miRNAs in COX-2 posttranscriprional regulation opens up the possibility to develop an endogenous silencing mechanism to knockdown overexpressed COX-2 during tumour cell evolution.