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细胞周期是细胞生命活动的基本过程,它控制着细胞从静止期转向生长增殖期。细胞周期蛋白依赖激酶(Cdks)和细胞周期蛋白(Cyclins)是整个细胞周期调控机制中的核心分子。细胞周期调控异常与细胞癌变密切相关,90%以上的肿瘤,尤其是胶质瘤和软组织肉瘤中Cdks都有过度表达。进一步分析指出,Cdks和Cyclins被作为治疗肿瘤的关键靶点,它们受抑制时能导致肿瘤细胞的死亡,抑制Cdks还能阻滞Cyclins转录。Ⅰ期临床研究提示,细胞周期素蛋白激酶抑制剂(CDKIs)有较高的安全性;Ⅱ期临床研究提示,CDKIs联合细胞毒性化疗药物作用肿瘤细胞有更好的前景,且CDKIs的使用剂量和时间顺序决定着其最佳使用效果。本文阐述了Cdks和Cyclins在肿瘤细胞周期中的表达,对Flavopiridol、Indisulam、AZD5438、SNS-032(BMS-387032)、Bryostatin-1、PD 0332991等CDKIs在肿瘤靶向性治疗中的研究作一综述。
Cell cycle is the basic process of cell life activities, it controls the cells from stationary phase to growth and proliferation phase. Cyclin-dependent kinases (Cdks) and cyclins (Cyclins) are the core molecules in the whole cell cycle regulatory mechanism. Abnormal cell cycle regulation is closely related to cell carcinogenesis. Over 90% of the tumors, especially glioma and soft tissue sarcoma, are overexpressed. Further analysis indicated that Cdks and Cyclins are the key targets for the treatment of tumors. When they are inhibited, they lead to the death of tumor cells, and inhibition of Cdks can also block the transcription of Cyclins. Phase I clinical studies suggest that cyclin protein kinase inhibitors (CDKIs) have a higher safety; phase Ⅱ clinical studies suggest that CDKIs combined with cytotoxic chemotherapy drugs have a better prospect of tumor cells, and the dose of CDKIs and The order of time determines its best effect. This article describes the expression of Cdks and Cyclins in tumor cell cycle and reviews the research of CDKIs in tumor targeting therapy such as Flavopiridol, Indisulam, AZD5438, SNS-032 (BMS-387032), Bryostatin-1 and PD 0332991 .