非整倍体
染色体分离
中心体
生物
主轴检查点
动细胞
染色体不稳定性
癌症研究
癌症
染色体
遗传学
细胞生物学
细胞周期
基因
作者
Masanori Kawakami,Xi Liu,Ethan Dmitrovsky
出处
期刊:Annual Review of Pharmacology and Toxicology
[Annual Reviews]
日期:2019-01-06
卷期号:59 (1): 361-377
被引量:23
标识
DOI:10.1146/annurev-pharmtox-010818-021649
摘要
Aneuploidy is a hallmark of cancer. Defects in chromosome segregation result in aneuploidy. Multiple pathways are engaged in this process, including errors in kinetochore-microtubule attachments, supernumerary centrosomes, spindle assembly checkpoint (SAC) defects, and chromosome cohesion defects. Although aneuploidy provides an adaptation and proliferative advantage in affected cells, excessive aneuploidy beyond a critical level can be lethal to cancer cells. Given this, enhanced chromosome missegregation is hypothesized to limit survival of aneuploid cancer cells, especially when compared to diploid cells. Based on this concept, proteins and pathways engaged in chromosome segregation are being exploited as candidate therapeutic targets for aneuploid cancers. Agents that induce chromosome missegregation and aneuploidy now exist, including SAC inhibitors, those that alter centrosome fidelity and others that are under active study in preclinical and clinical contexts. This review explores the therapeutic potentials of such new agents, including the benefits of combining them with other antineoplastic agents.
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