染色体不稳定性（CIN）是一种引发肿瘤异质性、表型适应性、药物抗性和预后不良的癌症标志。高级别浆液性卵巢癌（HGSOC）是最常见的染色体不稳定性肿瘤类型之一，其5年生存率仅为30％左右，主要原因是诊断晚和快速发展的药物抗性，例如通过CIN驱动的ABCB1易位。然而，CIN也是一个在细胞周期中易感性的问题，可以利用它来针对肿瘤细胞，这可以从PARP抑制剂成功针对同源重组缺陷（HRD）来进行说明。然而，缺乏适当的具有持续CIN的模型一直是完全利用特异性疾病CIN机制的一项障碍。这个障碍现在正在通过开发基于患者来源的细胞培养和器官样体来克服。在本综述中，我们描述了我们在建立一个包括120多个患者来源卵巢癌模型（OCMs）的活体库方面取得的进展，主要来自HGSOC。OCMs是高纯度的肿瘤分离物，具有广泛的增殖潜能，可以在早期通道中进行分析。OCMs具有多样的核型，表现出高于已建立的细胞系的细胞有丝分裂异常率的内部和患者间的异质性。OCMs涵盖了广泛的HGSOC标志，包括一系列p53变异和BRCA1/2突变，并且显示出临床上看到的药物抗性机制，例如ABCB1易位和BRCA2逆转。OCMs适用于功能分析、药物敏感性分析和多组学，包括单细胞的下一代测序，因此代表了描绘HGSOC特异性CIN机制的平台。反过来，我们的愿景是这种理解将有助于设计新的治疗策略。© 2023.作者。

Chromosome instability (CIN) is a cancer hallmark that drives tumour heterogeneity, phenotypic adaptation, drug resistance and poor prognosis. High-grade serous ovarian cancer (HGSOC), one of the most chromosomally unstable tumour types, has a 5-year survival rate of only ~30% - largely due to late diagnosis and rapid development of drug resistance, e.g., via CIN-driven ABCB1 translocations. However, CIN is also a cell cycle vulnerability that can be exploited to specifically target tumour cells, illustrated by the success of PARP inhibitors to target homologous recombination deficiency (HRD). However, a lack of appropriate models with ongoing CIN has been a barrier to fully exploiting disease-specific CIN mechanisms. This barrier is now being overcome with the development of patient-derived cell cultures and organoids. In this review, we describe our progress building a Living Biobank of over 120 patient-derived ovarian cancer models (OCMs), predominantly from HGSOC. OCMs are highly purified tumour fractions with extensive proliferative potential that can be analysed at early passage. OCMs have diverse karyotypes, display intra- and inter-patient heterogeneity and mitotic abnormality rates far higher than established cell lines. OCMs encompass a broad-spectrum of HGSOC hallmarks, including a range of p53 alterations and BRCA1/2 mutations, and display drug resistance mechanisms seen in the clinic, e.g., ABCB1 translocations and BRCA2 reversion. OCMs are amenable to functional analysis, drug-sensitivity profiling, and multi-omics, including single-cell next-generation sequencing, and thus represent a platform for delineating HGSOC-specific CIN mechanisms. In turn, our vision is that this understanding will inform the design of new therapeutic strategies.© 2023. The Author(s).