Preclinical and clinical studies have clearly shown a benefit of nonsteroidal anti-inflammatory drug (NSAID) use in reducing cancer risk. However, the adverse gastrointestinal and cardiovascular side effects associated with NSAIDs and COX-2 selective inhibitors (coxibs) have provoked more scrutiny of the precise role of specific downstream mediators in the prostaglandin (PG) signaling cascade. NSAIDs and coxibs inhibit PG biosynthesis. One of the PGs produced at high levels in the tumor microenvironment is PGE(2), which is thought to play a major role in cancer progression. Thus, a better understanding of PGE(2) signaling could enable identification of novel and safer therapeutic targets downstream of the cyclooxygenase enzymes. We review the emerging molecular mechanisms by which COX-2-derived PGE(2) is involved in cancer progression and delineate potential opportunities for development of novel pharmacologic approaches utilizing this pathway.

中文翻译：

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NSAID和癌症预防：靶向COX-2下游。

临床前和临床研究清楚地表明，使用非甾体抗炎药（NSAID）可以降低癌症风险。但是，与NSAID和COX-2选择性抑制剂（coxibs）相关的胃肠道和心血管不良反应引起了对特定下游介质在前列腺素（PG）信号级联反应中确切作用的更多审查。NSAID和coxib抑制PG的生物合成。在肿瘤微环境中高水平产生的PG之一是PGE（2），据认为在癌症进展中起主要作用。因此，对PGE（2）信号的更好的理解可以使环氧合酶酶下游的新型和更安全的治疗目标的鉴定。