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WEE1激酶是一种细胞周期调节蛋白,能调控细胞周期蛋白依赖性激酶1(cyclin-dependent kinase 1,CDK1)的磷酸化状态,从而调节CDK1与细胞周期蛋白B(cyclin B)复合物的活性从而实现对细胞周期的调控,且对DNA损伤检查点具有重要的调节作用。WEE1是G2/M期阻滞的关键基因,起着重要的监测作用,在一些癌症中过表达,抑制或下调WEE1激酶均能引发有丝分裂灾难,因此WEE1激酶抑制剂可能在抗癌治疗中有关键作用。在癌症的治疗过程中,WEE1抑制剂与DNA损伤剂、化学药物等联合使用会得到比单独使用更为有效,且在p53缺失的癌细胞中能发挥更好的效果。目前WEE1已成为许多癌症治疗的关键靶点之一,其抑制剂MK-1775已处于临床研究阶段,且能增强一些DNA损伤剂对p53缺失的癌细胞的杀伤能力。本文就WEE1激酶及其抑制剂在抗癌治疗中的应用作一综述。
WEE1 kinase is a cell cycle regulatory protein that regulates the phosphorylation status of cyclin-dependent kinase 1 (CDK1) and thus regulates the activity of CDK1 and cyclin B complexes to To achieve the regulation of the cell cycle, and DNA damage checkpoint has an important regulatory role. WEE1 is a key gene in G2 / M arrest and plays an important role in monitoring. In some cancers overexpression, inhibition or down-regulation of WEE1 kinase can trigger mitotic catastrophe, WEE1 kinase inhibitor may play a key role in anti-cancer therapy effect. In the treatment of cancer, WEE1 inhibitors in combination with DNA damaging agents, chemicals and the like will be more effective than single use and will be able to exert better effects in p53-deficient cancer cells. Currently, WEE1 has become one of the key targets of many cancer treatments. Its inhibitor MK-1775 has been in the clinical research stage and can enhance the killing ability of some DNA damaging agents on p53-deficient cancer cells. This review summarizes the applications of WEE1 kinase and its inhibitors in anti-cancer therapy.