Our observations suggested a suppression of DRAK2 expression, either directly or indirectly, by the actions of COX-2-derived prostaglandins in tumour samples. To test this hypothesis further, five patients with newly diagnosed CRC (not taking aspirin or NSAIDS) were recruited to a pilot study. Endoscopic biopsies of tumour tissue were obtained before and after a short course (5 -7 days) of treatment with the COX-2-selective inhibitor rofecoxib at a dose of 25 mg daily, a dose that has been demonstrated to selectively inhibit COX-2 in vivo (Ehrich et al, 1999) . The study was conducted before the withdrawal of rofecoxib by the manufacturer. qRT-PCR demonstrated an induction in DRAK2 expression ( Figure 4A ; mean 2.5-fold increase, P ¼ 0.01) in tumour from each of the patients treated with rofecoxib, reflective of the changes seen with COX-2 inhibition in vitro. The expression of a panel of additional genes was also evaluated for comparative purposes ( Figure 4B ). Although no significant change in several genes that modulate apoptosis (Bax, Bcl-xl) was observed, a significant decrease in VEGF expression was noted, with a mean reduction of close to 40% (P ¼ 0.01). This pro-angiogenic factor has previously been linked to COX-2 activity and reduced VEGF expression has been observed in animal models following treatment with rofecoxib (Yao et al, 2003) . This finding provided additional validation of the suppression of COX-2 activity in the tumours of these patients. 