Chromosomal instability (CIN) is a hallmark of cancer and a driver of metastatic dissemination, therapeutic resistance, and immune evasion. CIN is present in 60–80% of human cancers and poses a formidable therapeutic challenge as evidenced by the lack of clinically approved drugs that directly target CIN. This limitation in part reflects a lack of well-defined druggable targets as well as a dearth of tractable biomarkers enabling direct assessment and quantification of CIN in patients with cancer. Over the past decade, however, our understanding of the cellular mechanisms and consequences of CIN has greatly expanded, revealing novel therapeutic strategies for the treatment of chromosomally unstable tumours as well as new methods of assessing the dynamic nature of chromosome segregation errors that define CIN. In this Review, we describe advances that have shaped our understanding of CIN from a translational perspective, highlighting both challenges and opportunities in the development of therapeutic interventions for patients with chromosomally unstable cancers.

染色体不稳定性 (CIN) 是癌症的一个标志，也是转移扩散、治疗耐药和免疫逃避的驱动因素。 CIN 存在于 60-80% 的人类癌症中，并带来了巨大的治疗挑战，缺乏临床批准的直接针对 CIN 的药物就证明了这一点。这种限制部分反映了缺乏明确的药物靶标，以及缺乏可直接评估和量化癌症患者 CIN 的易处理生物标志物。然而，在过去的十年中，我们对 CIN 的细胞机制和后果的理解已经大大扩展，揭示了治疗染色体不稳定肿瘤的新治疗策略，以及评估定义 CIN 的染色体分离错误的动态性质的新方法。在这篇综述中，我们描述了从转化角度理解 CIN 的进展，强调了为染色体不稳定癌症患者开发治疗干预措施的挑战和机遇。