细胞周期蛋白依赖性激酶调节剂：用于癌症治疗的一类新型细胞周期调节剂。

Cyclin-dependent kinase modulators: a novel class of cell cycle regulators for cancer therapy.

作者信息

Senderowicz A M

机构信息

Molecular Therapeutics Unit, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research National Institutes of Health, Building 30, Room 211, 30 Convent Drive, Bethesda, MD 20892-4340, USA.

出版信息

Cancer Chemother Biol Response Modif. 2001;19:165-88.

PMID:11686013

Abstract

With the understanding of the role of cdks in cell cycle regulation and the discovery that approx. 90% of all neoplasias are the result of 'cdk hyperactivation' leading to the abrogation of the Rb pathway, novel ATP competitive cdk inhibitors are being developed. The first two tested in clinical trials, flavopiridol and UCN-01, showed promising results with evidence of antitumor activity and plasma concentrations sufficient to inhibit cdk-related functions. Best schedule to be administered, combination with standard chemotherapeutic agents and demonstration of cdk modulation from tumor samples from patients in these trials are important issues that need to be answered in order to obtain the best possible results with these agents.

摘要

随着对细胞周期蛋白依赖性激酶（cdks）在细胞周期调控中作用的认识，以及发现约90%的肿瘤形成是“cdk过度激活”导致Rb通路废除的结果，新型ATP竞争性cdk抑制剂正在研发中。在临床试验中测试的前两种药物，即黄酮哌啶醇和UCN - 01，显示出了有前景的结果，有抗肿瘤活性的证据以及足以抑制cdk相关功能的血浆浓度。给药的最佳方案、与标准化疗药物的联合使用以及在这些试验中患者肿瘤样本中cdk调节的证明，都是为了用这些药物获得最佳可能结果而需要回答的重要问题。