Chen W, Qiu J, Shen Y M
School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
Drug Discov Ther. 2012 Oct;6(5):230-7.
DNA topoisomerase II (TOP2) is a well-known anticancer target. Its inhibitors are among the most effective anticancer drugs currently in clinical use. TOP2-targeting agents fall into two major classes of "Topo poisons" and "Topo inhibitors" based on their mechanisms of action. Mammalian cells possess two genetically distinct TOP2 isoforms, TOP2α and TOP2β, that are differentially regulated and play different roles in living cells. Compared to TOP2β, TOP2α may be an efficacious and safe chemotherapeutic target for cancer treatment. This review discusses the advantage of targeting TOP2α over TOP2β and action of various agents on TOP2α.
DNA拓扑异构酶II（TOP2）是一个著名的抗癌靶点。其抑制剂是目前临床使用的最有效的抗癌药物之一。基于作用机制，靶向TOP2的药物可分为两大类，即“拓扑毒物”和“拓扑抑制剂”。哺乳动物细胞具有两种基因不同的TOP2亚型，TOP2α和TOP2β，它们受到不同的调控，在活细胞中发挥不同的作用。与TOP2β相比，TOP2α可能是癌症治疗中一个有效且安全的化疗靶点。本文综述了靶向TOP2α相对于TOP2β的优势以及各种药物对TOP2α的作用。
