细胞周期蛋白依赖性激酶8及其抑制剂在抗肿瘤治疗中的研究进展

Cyclin-dependent kinase 8 and its inhibitors in antitumor therapy:research advances

细胞周期蛋白依赖性激酶8(CDK8)通过与中介体复合物结合或磷酸化相关转录因子以调节转录过程。相关研究报道,过度表达的CDK8通过激活Wnt-β-连环蛋白、促进雌激素诱导基因的转录和抑制超级增强子相关基因的表达,导致结直肠癌、乳腺癌和血液系统恶性肿瘤的发生。这些研究表明,CDK8是一个潜在的抗肿瘤靶点。本文首先概述CDK8的生物学功能及其在肿瘤发生中的作用机制,重点介绍CDK8抑制剂的研究进展,以期为后续靶向CDK8治疗癌症提供参考。

Cyclin-dependent kinase 8(CDK8)regulates transcription by binding to mediator complex or phosphorylating transcriptional factors. Recent studies have reported that overexpressed CDK8 leads to the development of colorectal cancer,breast cancer and hematological malignancies by activating Wnt-β-catenin,promoting the transcription of estrogen-inducible genes and inhibiting the expression of super enhancer-associated genes. These studies have indicated that CDK8 is a potential antitumor target. This paper briefly discusses the biological function of CDK8 and the regulatory mechanism of CDK8 on the tumorigenesis and its development,and reviews on the research progress in CDK8 inhibitors,hoping to provide a reference CDK8-targeting cancer therapy.