Cyclooxygenase-2 and cancer treatment: understanding the risk should be worth the reward.
Cyclooxygenase-2 and cancer treatment: understanding the risk should be worth the reward.
复制标题
DOI：
10.1158/1078-0432.ccr-09-0788
复制
发表时间：
2010-03-01
期刊：
影响因子：
--
通讯作者：
DuBois RN
中科院分区：
文献类型：
--
作者：
Menter DG;Schilsky RL;DuBois RN
靶向前列腺素（PG）通路可能是预防和治疗癌症的关键干预措施。前列腺素生物合成的中心是环氧合酶的两种同工型（考克斯1和2），其从质膜储存的脂肪酸产生前列腺素H2（PGH 2）。考克斯-1是组成型表达的，而考克斯-2是在许多癌症中上调的诱导型同种型。考克斯-1和考克斯-2催化位点之间的差异使得能够开发选择性抑制剂。在考克斯酶的下游，前列腺素E2合酶将可用的PGH 2转化为前列腺素E2（PGE 2），其可以刺激癌症进展。重要的研究工作有助于确定更多的选择性靶点，并充分阐明前列腺素E2介导的肿瘤发生的下游靶点。尽管如此，作为PG生物合成的关键限速控制点，考克斯-2仍然是重要的抗癌靶点。随着我们进入个体化医学的新时代，对考克斯-2选择性靶向治疗的个体风险/获益的更好理解正在迅速发展。本文综述了考克斯-2及其下游靶点作为抗癌研究的重要领域的进展，并提供了分子医学的一个令人兴奋的方面的现状。
Targeting the prostaglandin (PG) pathway is potentially a critical intervention for the prevention and treatment of cancer. Central to prostaglandin biosynthesis are two isoforms of cyclooxygenase (COX 1 and 2), which produce prostaglandin H2 (PGH2) from plasma membrane stores of fatty acids. COX-1 is constitutively expressed while 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 E2 synthase converts available PGH2 to prostaglandin E2 (PGE2), which can stimulate cancer progression. Significant research efforts are helping identify more selective targets and fully elucidate the downstream targets of prostaglandin E2 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/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 anti-cancer research and to provide the current status of an exciting aspect of molecular medicine.