Mills Christopher C, Kolb E A, Sampson Valerie B
University of Delaware, Newark, Delaware.
Nemours Center for Cancer and Blood Disorders, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware.
Cancer Res. 2017 Dec 1;77(23):6489-6498. doi: 10.1158/0008-5472.CAN-17-2066. Epub 2017 Nov 2.
This review describes the pivotal roles of cell-cycle and checkpoint regulators and discusses development of specific cell-cycle inhibitors for therapeutic use for pediatric cancer. The mechanism of action as well as the safety and tolerability of drugs in pediatric patients, including compounds that target CDK4/CDK6 (palbociclib, ribociclib, and abemaciclib), aurora kinases (AT9283 and MLN8237), Wee1 kinase (MK-1775), KSP (ispinesib), and tubulin (taxanes, vinca alkaloids), are presented. The design of mechanism-based combinations that exploit the cross-talk of signals activated by cell-cycle arrest, as well as pediatric-focused drug development, are critical for the advancement of drugs for rare childhood diseases. .
本综述描述了细胞周期和检查点调节因子的关键作用，并讨论了用于儿科癌症治疗的特定细胞周期抑制剂的研发情况。文中介绍了药物在儿科患者中的作用机制以及安全性和耐受性，包括靶向CDK4/CDK6的化合物（哌柏西利、瑞博西尼和阿贝西利）、极光激酶（AT9283和MLN8237）、Wee1激酶（MK-1775）、KSP（艾司西肽素）和微管蛋白（紫杉烷类、长春花生物碱）。利用细胞周期阻滞激活的信号相互作用的基于机制的联合用药设计以及针对儿科的药物研发，对于罕见儿童疾病药物的进展至关重要。
