Department of Cancer Biology and GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Clin Cancer Res. 2010 Mar 1;16(5):1384-90. doi: 10.1158/1078-0432.CCR-09-0788. Epub 2010 Feb 23.
Targeting the prostaglandin (PG) pathway is potentially a critical intervention for the prevention and treatment of cancer. Central to PG biosynthesis are two isoforms of cyclooxygenase (COX 1 and 2), which produce prostaglandin H(2) (PGH(2)) from plasma membrane stores of fatty acids. COX-1 is constitutively expressed, whereas COX-2 is an inducible isoform upregulated in many cancers. Differences between COX-1 and COX-2 catalytic sites enabled development of selective inhibitors. Downstream of the COX enzymes, prostaglandin E(2) synthase converts available PGH(2) to prostaglandin E(2) (PGE(2)), which can stimulate cancer progression. Significant research efforts are helping identify more selective targets and fully elucidate the downstream targets of prostaglandin E(2)-mediated oncogenesis. Nonetheless, as a key rate-limiting control point of PG biosynthesis, COX-2 continues to be an important anticancer target. As we embark upon a new era of individualized medicine, a better understanding of the individual risk and/or benefit involved in COX-2 selective targeting is rapidly evolving. This review endeavors to summarize developments in our understanding of COX-2 and its downstream targets as vital areas of anticancer research and to provide the current status of an exciting aspect of molecular medicine.
靶向前列腺素（PG）途径可能是预防和治疗癌症的关键干预措施。PG 生物合成的核心是两种环氧化酶（COX1 和 COX2）同工型，它们从脂肪酸的质膜储存中产生前列腺素 H2（PGH2）。COX1 是组成型表达的，而 COX2 是许多癌症中上调的诱导型同工型。COX1 和 COX2 催化位点之间的差异使选择性抑制剂得以开发。在 COX 酶的下游，前列腺素 E2 合酶将可用的 PGH2 转化为前列腺素 E2（PGE2），从而可以刺激癌症进展。大量的研究工作正在帮助识别更具选择性的靶点，并充分阐明前列腺素 E2 介导的致癌作用的下游靶点。尽管如此，作为 PG 生物合成的关键限速控制点，COX-2 仍然是一个重要的抗癌靶点。随着我们进入个体化医学的新时代，对 COX-2 选择性靶向涉及的个体风险和/或获益的理解正在迅速发展。本综述旨在总结我们对 COX-2 及其下游靶点的理解，这些靶点是抗癌研究的重要领域，并提供分子医学令人兴奋的方面的现状。
