Chromosomal instability and cancer: a complex relationship with therapeutic potential
Chromosomal instability and cancer: a complex relationship with therapeutic potential
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DOI：
10.1172/jci59954
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发表时间：
2012-04-01
影响因子：
15.9
通讯作者：
Compton, Duane A.
中科院分区：
文献类型：
--
作者：
Bakhoum, Samuel F.;Compton, Duane A.
染色体不稳定(CIN)是人类肿瘤的一个特征。尽管它广泛流行，但对CIN在癌症中的机制和作用的了解一直是难以捉摸的。现在很明显，CIN在肿瘤启动和生长中的作用比之前认为的要复杂得多。此外，区分CIN和非整倍体对于理解它们各自在癌症中的作用是至关重要的。CIN包括染色体错误分离率升高，而非整倍体是染色体数量异常的一种状态。总的来说，实验证据表明，CIN通过允许肿瘤不断采样非整倍体适应环境而使肿瘤适应。这种复杂的关系，加上可能在药物上影响癌细胞中的染色体错误分离频率，提供了以前未被认识到的限制肿瘤生长及其对治疗的反应的方法。
Chromosomal instability (CIN) is a hallmark of human neoplasms. Despite its widespread prevalence, knowledge of the mechanisms and contributions of CIN in cancer has been elusive. It is now evident that the role of CIN in tumor initiation and growth is more complex than previously thought. Furthermore, distinguishing CIN, which consists of elevated rates of chromosome missegregation, from aneuploidy, which is a state of abnormal chromosome number, is crucial to understanding their respective contributions in cancer. Collectively, experimental evidence suggests that CIN enables tumor adaptation by allowing tumors to constantly sample the aneuploid fitness landscape. This complex relationship, together with the potential to pharmacologically influence chromosome missegregation frequencies in cancer cells, offers previously unrecognized means to limit tumor growth and its response to therapy.