Traditional NSAIDs have anti-neoplastic properties, but their prolonged use is limited by their association with gastrointestinal side effects, particularly the risk of gastrointestinal haemorrhage. The new-generation coxibs have also shown promise for chemoprevention of CRC but are now considered by many to carry an unacceptable risk of thrombotic events. Our aim was to identify novel 'effector' pathways operating downstream of COX-2 in tumours, so that this knowledge might allow future selection of more refined therapeutic targets.