Aberrant chromosomal architecture, ranging from small insertions or deletions to large chromosomal alterations, is one of the most common characteristics of cancer genomes. Chromosomal instability (CIN) underpins much of the intratumoural heterogeneity observed in cancers and drives phenotypic adaptation during tumour evolution. Thus, an urgent need exists to increase our efforts to target CIN as if it were a molecular entity. Indeed, CIN accelerates the development of anticancer drug resistance, often leading to treatment failure and disease recurrence, which limit the effectiveness of most current therapies. Identifying novel strategies to modulate CIN and to exploit the fitness cost associated with aneuploidy in cancer is, therefore, of paramount importance for the successful treatment of cancer. Modern sequencing and analytical methods greatly facilitate the identification and cataloguing of somatic copy-number alterations and offer new possibilities to better exploit the dynamic process of CIN. In this Review, we describe the principles governing CIN propagation in cancer and how CIN might influence sensitivity to immune-checkpoint inhibition, and survey the vulnerabilities associated with CIN that offer potential therapeutic opportunities.

异常的染色体结构，从小的插入或缺失到大的染色体改变，是癌症基因组最常见的特征之一。染色体不稳定性（CIN）是癌症中观察到的大部分肿瘤内异质性的基础，并驱动肿瘤进化过程中的表型适应。因此，迫切需要加大力度针对 CIN，就像它是一个分子实体一样。事实上，CIN 加速了抗癌药物耐药性的发展，常常导致治疗失败和疾病复发，从而限制了大多数当前疗法的有效性。因此，确定调节 CIN 并利用与癌症非整倍性相关的适应成本的新策略对于成功治疗癌症至关重要。现代测序和分析方法极大地促进了体细胞拷贝数改变的识别和编目，并为更好地利用 CIN 的动态过程提供了新的可能性。在这篇综述中，我们描述了控制癌症中 CIN 传播的原则以及 CIN 如何影响对免疫检查点抑制的敏感性，并调查了与 CIN 相关的脆弱性，从而提供了潜在的治疗机会。