Chromosomal instability (CIN) is a hallmark of cancer and is associated with tumor cell malignancy. CIN triggers a chain reaction in cells leading to chromosomal abnormalities, including deviations from the normal chromosome number or structural changes in chromosomes. CIN arises from errors in DNA replication and chromosome segregation during cell division, leading to the formation of cells with abnormal number and/or structure of chromosomes. Errors in DNA replication result from abnormal replication licensing as well as replication stress, such as double-strand breaks and stalled replication forks; meanwhile, errors in chromosome segregation stem from defects in chromosome segregation machinery, including centrosome amplification, erroneous microtubule–kinetochore attachments, spindle assembly checkpoint, or defective sister chromatids cohesion. In normal cells, CIN is deleterious and is associated with DNA damage, proteotoxic stress, metabolic alteration, cell cycle arrest, and senescence. Paradoxically, despite these negative consequences, CIN is one of the hallmarks of cancer found in over 90% of solid tumors and in blood cancers. Furthermore, CIN could endow tumors with enhanced adaptation capabilities due to increased intratumor heterogeneity, thereby facilitating adaptive resistance to therapies; however, excessive CIN could induce tumor cells death, leading to the “just-right” model for CIN in tumors. Elucidating the complex nature of CIN is crucial for understanding the dynamics of tumorigenesis and for developing effective anti-tumor treatments. This review provides an overview of causes and consequences of CIN, as well as the paradox of CIN, a phenomenon that continues to perplex researchers. Finally, this review explores the potential of CIN-based anti-tumor therapy.

染色体不稳定性（CIN）是癌症的一个标志，与肿瘤细胞恶性肿瘤有关。 CIN 会在细胞中引发连锁反应，导致染色体异常，包括偏离正常染色体数量或染色体结构变化。 CIN 是由细胞分裂过程中 DNA 复制和染色体分离错误引起的，导致形成染色体数量和/或结构异常的细胞。 DNA复制错误是由异常复制许可和复制压力造成的，例如双链断裂和复制叉停滞；同时，染色体分离的错误源于染色体分离机制的缺陷，包括中心体扩增、错误的微管-着丝粒附着、纺锤体组装检查点或有缺陷的姐妹染色单体凝聚力。在正常细胞中，CIN 是有害的，并与 DNA 损伤、蛋白毒性应激、代谢改变、细胞周期停滞和衰老有关。矛盾的是，尽管存在这些负面后果，CIN 却是 90% 以上的实体瘤和血癌中发现的癌症标志之一。此外，由于肿瘤内异质性增加，CIN可以赋予肿瘤增强的适应能力，从而促进对治疗的适应性抵抗；然而，过量的 CIN 可能会诱导肿瘤细胞死亡，从而导致肿瘤中 CIN 的“恰到好处”模型。阐明 CIN 的复杂性质对于了解肿瘤发生的动态和开发有效的抗肿瘤治疗至关重要。这篇综述概述了 CIN 的原因和后果，以及 CIN 的悖论，这一现象一直困扰着研究人员。最后，本综述探讨了基于 CIN 的抗肿瘤治疗的潜力。