Abstract
Despite recent improvements in chemotherapy and radiation therapy in cancer management with the addition of biological agents, novel treatment approaches are needed to further benefit patients. Cyclo-oxygenase (COX)-2 inhibition represents one such possibility. COX-2 is an enzyme induced in pathological states such as inflammatory disorders and cancer, where it mediates production of prostanoids. The enzyme is commonly expressed in both premalignant lesions and malignant tumours of different types. A growing body of evidence suggests an association of COX-2 with tumour development, aggressive biological tumour behaviour, resistance to standard cancer treatment, and adverse patient outcome. COX-2 may be related to cancer development and propagation through multiple mechanisms, including stimulation of growth, migration, invasiveness, resistance to apoptosis, suppression of the immunosurveillance system, and enhancement of angiogenesis. Epidemiological data suggest that NSAIDs and selective COX-2 inhibitors might prevent the development of cancers, including colorectal, oesophageal and lung cancer. Preclinical investigations have demonstrated that inhibition of this enzyme with selective COX-2 inhibitors enhances tumour response to radiation and chemotherapeutic agents. These preclinical findings have been rapidly advanced to clinical oncology. Clinical trials of the combination of selective COX-2 inhibitors with radiotherapy, chemotherapy or both in patients with a number of cancers have been initiated, and preliminary results are encouraging. This review discusses the role of COX-2, its products (prostaglandins) and its inhibitors in tumour growth and treatment.
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Acknowledgements
No sources of funding were used to assist in the preparation of this review. Dr Mason and Dr Milas have licensed their patent on combination of a COX-2 inhibitor and radiation for the treatment of neoplasia to Pfizer Inc. and receive royalities from Pfizer Inc. Dr Liao has no potential conflicts of interest directly relevant to the content of this review.
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Liao, Z., Mason, K.A. & Milas, L. Cyclo-Oxygenase-2 and its Inhibition in Cancer. Drugs 67, 821–845 (2007). https://doi.org/10.2165/00003495-200767060-00001
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DOI: https://doi.org/10.2165/00003495-200767060-00001