WEE1 激酶及其抑制剂在抗肿瘤治疗中的应用进展

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。

Progress in WEE1 Kinase and Its Inhibitor for Anticancer Therapy

WEE1 kinase is a kind of cell cycle regulatory proteins. It can control the phosphorylation status of CDK1 so as to regulate the activity of CDK1 and Cyclin B complex to realize the regulation of cell cycle. WEE1 kinase plays an important role for DNA damage checkpoint. WEE1 kinase is important to the G2 /Mphase and is overexpression in some cancer. Inhibition or downregulation of WEE1 kinase could trigger the mitotic catastrophe". Therefore, WEE1 kinase inhibitors may have a key role in anticancer therapy. In the process of the treatment of cancer, the combination of WEE1 inhibitors with DNA damage agents can be more effective than those of monotherapy, and in the loss of p53 cancer cells can play a better effect. At present, it has become one of the key targets for many cancer therapy, its inhibitor MK-1775 has been in clinical research stage, and it can enhance the killing ability of some DNA damaging agents against the loss of p53 cancer cells. This paper reviewed progress in WEE1 kinase and its inhibitor for anticancer therapy.