COX-2 inhibitors in breast cancer

[摘要] The cyclooxygenase (COX) enzymes catalyse the rate-limiting step of conversion from arachidonic acid to prostaglandins (PGs). The enzyme exists in two isoforms COX-1 and COX-2. The inducible COX-2 isoform has been shown to be present in up to 80% of breast cancers, high expression correlating with low rates of apoptosis, increased angiogenesis and poor prognosis. Both non-steroidal anti-inflammatory drugs (NSAIDs) and selective inhibitors to COX-2 have been associated with anti-tumoural properties, decreasing the rates of tumour growth, increasing apoptosis and inhibiting angiogenesis. A variety of cellular mechanisms have been suggested, but the exact mechanisms of action remain unclear. COX-2 inhibitors have the potential to be used either alone, or in combination with other agents such as aromatase inhibitors (AIs), monoclonal antibodies (i.e. trastuzumab) or chemotherapeutic agents as novel therapeutic strategies against breast cancer. However the potential cardiac toxicity of the COX-2 selective compounds needs to be fully addressed, with the future development of either safe dosing regimes or new compounds.

[学科分类] 肿瘤学