Commentary The COX and LOX products of n-6 fatty acid metabolism may exert stimulatory effects on cancer progression at several levels, and in this review we have presented published data in support of a role in tumor-mediated angio-genesis. In addition, these eicosanoids can modulate tumor cell growth and invasion directly and promote the intra-vascular steps of the metastatic cascade [42,55,56,103]. Thus the multiple events contributing to aggressive tumor behavior may be enhanced indirectly by n-6 fatty acids and directly by the eicosanoids derived from them and suppressed by the n-3 fatty acids and pharmacological inhibitors of eicosanoid biosynthesis. Experimentally, dietary n-3 fatty acids inhibit the growth of preexisting breast cancer micrometastases when used as adjuvant nutritional therapy after excision of the primary tumor, and most likely the suppression of angiogenesis contributes to this therapeutic effect [48]. Elsewhere, we have discussed in detail the potential for dietary n-3 fatty acid supplementation as an adjunct to surgery and conventional combination chemotherapy and for cancer prevention [113,114]. Overall, a review of the published experimental studies indicates that selective pharmacological inhibitors of COX and LOX activity and dietary n-3 fatty acid supple-mentation should be included in future clinical trials and that the biological rationale rests, in part, on their antiangiogenic effects. In addition to its involvement in cancer progression, COX-2-mediated angiogenesis most likely has a critical role in the progression of preneoplastic lesions to the invasive phenotype. Thus the angiogenic process itself [12-16] and COX-2 expression [54,114,115] have been associated with carcinogenesis, indicating that pharmacological inhibitors of the isozyme may exert their cancer chemopreventive effects by mechanisms that include antiangiogenic activity. 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