Modulating Cell Cycle: Current Applications and Prospects for Future Drug Development
Modulating Cell Cycle: Current Applications and Prospects for Future Drug Development
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DOI：
10.2174/1568009023333809
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发表时间：
2002-01-01
影响因子：
3
通讯作者：
Bakkar, Nadine
中科院分区：
文献类型：
--
作者：
Gali-Muhtasib, Hala;Bakkar, Nadine
细胞周期是一组高度保守且有序的事件，最终导致细胞生长和分裂。它受到许多允许或限制其进展的监管机制的严格控制。在控制细胞周期进展中发挥关键作用的主要调节蛋白家族是细胞周期蛋白、细胞周期蛋白依赖性激酶 (Cdks)、其底物蛋白、Cdk 抑制剂 (CKI) 以及肿瘤抑制基因产物 p53 和 pRb。许多细胞周期控制基因一旦失调，就会导致不分裂的细胞进入细胞周期并开始增殖，从而导致癌症的发生。它们通过与基本细胞周期调节机制相互作用来激活细胞周期进入来实现这一点。目前，人们对寻找调节细胞周期调节分子的抗癌药物治疗策略的可能性非常乐观。此类策略的候选目标包括参与 G(1) 至 S 期或 G(2) 至 M 期转变的关键细胞周期分子。这篇综述将概述负责催化细胞周期进入的基本调控机制，并描述细胞周期调控领域的最新进展。将讨论以细胞周期特别是 Cdks 为靶标作为开发新颖、特异且可能更有效的抗癌治疗方法的基础。将提供正在进行或接近进行临床试验的新型细胞周期靶向剂的示例。
The cell cycle is a highly conserved and ordered set of events, culminating in cell growth and division. It is tightly controlled by many regulatory mechanisms that either permit or restrain its progression. The main families of regulatory proteins that play key roles in controlling cell cycle progression are the cyclins, the cyclin dependent kinases (Cdks), their substrate proteins, the Cdk inhibitors (CKI) and the tumor suppressor gene products, p53 and pRb. Many cell cycle control genes, when deregulated, can cause cells that are not dividing to enter the cell cycle and begin to proliferate leading to cancer development. They do so by interfacing with the basic cell cycle-regulatory machinery to activate cell cycle entry. There is at present much optimism about the possibility of finding anticancer drug treatment strategies that modulate cell cycle regulatory molecules. Candidate targets for such strategies include crucial cell cycle molecules involved in G(1) to S phase or G(2) to M phase transition. This review will outline the basic regulatory machinery responsible for catalyzing cell cycle entry and describe the latest advances made in the field of cell cycle regulation. The basis of targeting the cell cycle particularly the Cdks as an approach to developing novel, specific and perhaps more effective anticancer treatments will be discussed. Examples of novel cell cycle-targeting agents that are in, or are close to being in clinical trials will be provided.