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首页> 外文期刊>Cell cycle >Unleashing Chk1 in cancer therapy.
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Unleashing Chk1 in cancer therapy.

机译：在癌症治疗中释放Chk1。

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摘要

The checkpoint kinase 1 (Chk1) is one of the major players in the signal transduction pathway set in motion in response to DNA damage which activates different cell cycle checkpoints including the G 1/S, the intra-S, G 2-M and the mitotic spindle checkpoint, contributing to the maintenance of genomic stability. Chk1 is considered a good molecular target to inhibit, in combination with other anticancer agents, to increase the sensitivity of treatment, especially in tumors with a defective G 1 checkpoint. Experimental evidence highlights the essential role of Chk1 in normal and cancer cells even under unstressed conditions, especially in controlling DNA replication and cell division. This review looks at the main functions of Chk1 and the data on Chk1 inhibitors at their preclinical and clinical development are reported. This information may suggest novel approaches for new treatments with Chk1 inhibitors in combination with anticancer agents or as single agents. The emergent synthetic lethality approach may help define the genetic background features where Chk1 inhibitors alone could be very effective.
机译：检查点激酶1（Chk1）是响应DNA损伤而启动的信号转导通路中的主要参与者之一，DNA激活了不同的细胞周期检查点，包括G 1 / S，S内，G 2-M和有丝分裂纺锤体检查点，有助于维持基因组稳定性。 Chk1被认为是与其他抗癌药合用抑制药物，以提高治疗敏感性的良好分子靶标，尤其是在G 1检查点缺陷的肿瘤中。实验证据突显了Chk1在正常细胞和癌细胞中的重要作用，即使在不受压力的条件下，尤其是在控制DNA复制和细胞分裂方面。这篇综述着眼于Chk1的主要功能，并报道了Chk1抑制剂在其临床前和临床开发中的数据。该信息可能提示用Chk1抑制剂与抗癌药联合或作为单药联合治疗的新方法。新兴的合成杀伤性方法可能有助于定义仅Chk1抑制剂可能非常有效的遗传背景特征。

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