有丝分裂激酶抑制剂在胃肠道肿瘤中的治疗潜力

Aadil Javed, Gianluca Malagraba, M. Yarmohammadi, Catalina M. Perelló-Reus, C. Barceló, Teresa Rubio-Tomás
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引用次数: 3

摘要

有丝分裂需要维持所有分裂细胞基因组完整性所需的机制变化。这个过程是复杂的,并且在时间和空间上受到一系列有序的蛋白激酶的激活和失活的调节。有丝分裂激酶确保在细胞周期的G2期之后逐步进入有丝分裂,随后是前期、中期、中期、后期、末期,以及随后的细胞分裂和两个具有相同分离和基因组分布的子细胞的诞生。主要的有丝分裂激酶包括细胞周期蛋白依赖性激酶1 (CDK1)、极光激酶A和B激酶以及polo样激酶1 (PLK1)等。由于有丝分裂保真度和基因组完整性相互关联并依赖于这些调节因子,因此在许多癌症中已经报道了这些激酶的过表达,这些因子的天然不规则性可以作为各种癌症的治疗策略。在这里,我们报告并总结了最近关于各种靶向激酶的有丝分裂抑制剂的最新文献,这些抑制剂可以作为胃肠道癌症(包括胃癌、肝癌、胰腺癌和结直肠癌)的潜在治疗干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Therapeutic Potential of Mitotic Kinases’ Inhibitors in Cancers of the Gastrointestinal System
Mitosis entails mechanistic changes required for maintaining the genomic integrity in all dividing cells. The process is intricate and temporally and spatially regulated by the ordered series of activation and de-activation of protein kinases. The mitotic kinases ensure the stepwise progression of entry into mitosis after the G2 phase of the cell cycle, followed by prophase, pro-metaphase, metaphase, anaphase, telophase, and subsequently cytokinesis and birth of two daughter cells with equal segregation and distribution of the genome. The major mitotic kinases include cyclin-dependent kinase 1 (CDK1), Aurora A and B Kinases, and Polo-Like-Kinase 1 (PLK1), among others. Overexpression of some of these kinases has been reported in many cancers as the mitotic fidelity and genome integrity are interlinked and dependent on these regulators, the native irregularities in these factors can be targeted as therapeutic strategies for various cancers. Here, we report and summarize the recent updates on the literature describing the various mitotic inhibitors targeting kinases, which can be used as potential therapeutic interventions for gastrointestinal cancers including gastric cancer, liver cancer, pancreatic cancer and colorectal cancer.
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