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极光激酶在头颈部癌症中的治疗靶点。

Aurora Kinases as Therapeutic Targets in Head and Neck Cancer.

出版信息

Cancer J. 2022;28(5):387-400. doi: 10.1097/PPO.0000000000000614.

Abstract

The Aurora kinases (AURKA and AURKB) have attracted attention as therapeutic targets in head and neck squamous cell carcinomas. Aurora kinases were first defined as regulators of mitosis that localization to the centrosome (AURKA) and centromere (AURKB), governing formation of the mitotic spindle, chromatin condensation, activation of the core mitotic kinase CDK1, alignment of chromosomes at metaphase, and other processes. Subsequently, additional roles for Aurora kinases have been defined in other phases of cell cycle, including regulation of ciliary disassembly and DNA replication. In cancer, elevated expression and activity of Aurora kinases result in enhanced or neomorphic locations and functions that promote aggressive disease, including promotion of MYC expression, oncogenic signaling, stem cell identity, epithelial-mesenchymal transition, and drug resistance. Numerous Aurora-targeted inhibitors have been developed and are being assessed in preclinical and clinical trials, with the goal of improving head and neck squamous cell carcinoma treatment.

摘要

极光激酶(AURKA 和 AURKB)已作为头颈部鳞状细胞癌的治疗靶点引起了关注。极光激酶最初被定义为有丝分裂的调节剂,其定位于中心体(AURKA)和着丝粒(AURKB),调节纺锤体的形成、染色质的浓缩、核心有丝分裂激酶 CDK1 的激活、中期染色体的排列以及其他过程。随后,在细胞周期的其他阶段也定义了极光激酶的其他作用,包括对纤毛解体和 DNA 复制的调节。在癌症中,极光激酶的表达和活性升高导致增强或新的位置和功能,促进侵袭性疾病,包括促进 MYC 表达、致癌信号、干细胞特性、上皮-间充质转化和耐药性。已经开发了许多针对极光激酶的抑制剂,并正在进行临床前和临床试验评估,旨在改善头颈部鳞状细胞癌的治疗。

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