卵巢癌的特征是染色体不稳定。新的治疗方案可以改善相关表型的患者预后，然而治疗耐受性和长期生存指标要求更好的患者预选。受损的DNA损伤应答（DDR）是主要的化疗敏感性决定因素。由五个通路组成的DDR冗余是复杂的，很少同时研究与线粒体功能障碍引起的化疗耐受性影响。我们开发了功能性测定来监测DDR和线粒体状态，并在患者培养物上进行了试验。我们对16名接受铂类化疗的原发性卵巢癌患者的文化中进行了DDR和线粒体特征分析。通过多个统计和机器学习方法评估了实体特征与患者无进展生存期（PFS）和总生存期（OS）之间的关系。DR失调非常广泛。HR缺陷（HRD）和NHEJ几乎是互斥的。HRD患者（44％）有增加的SSB消融。HR能力与紊乱的线粒体有关（78％对57％的HRD），而每个复发患者都有线粒体功能障碍。DDR特征分类了实体铂类细胞毒作用和线粒体失调。重要的是，实体特征分类了患者的PFS和OS。虽然个别通路分数在机械上不足以描述耐受性，但整体DDR和线粒体状态可以准确预测患者的生存期。我们的测定套件展示了转化化疗敏感性预测的前景。©2023年。作者。

Ovarian cancers are hallmarked by chromosomal instability. New therapies deliver improved patient outcomes in relevant phenotypes, however therapy resistance and poor long-term survival signal requirements for better patient preselection. An impaired DNA damage response (DDR) is a major chemosensitivity determinant. Comprising five pathways, DDR redundancy is complex and rarely studied alongside chemoresistance influence from mitochondrial dysfunction. We developed functional assays to monitor DDR and mitochondrial states and trialled this suite on patient explants.We profiled DDR and mitochondrial signatures in cultures from 16 primary-setting ovarian cancer patients receiving platinum chemotherapy. Explant signature relationships to patient progression-free (PFS) and overall survival (OS) were assessed by multiple statistical and machine-learning methods.DR dysregulation was wide-ranging. Defective HR (HRD) and NHEJ were near-mutually exclusive. HRD patients (44%) had increased SSB abrogation. HR competence was associated with perturbed mitochondria (78% vs 57% HRD) while every relapse patient harboured dysfunctional mitochondria. DDR signatures classified explant platinum cytotoxicity and mitochondrial dysregulation. Importantly, explant signatures classified patient PFS and OS.Whilst individual pathway scores are mechanistically insufficient to describe resistance, holistic DDR and mitochondrial states accurately predict patient survival. Our assay suite demonstrates promise for translational chemosensitivity prediction.© 2023. The Author(s).