虽然无细胞液体活检（cfLB）方法提供简单且廉价的疾病监测，但基于细胞的液体活检（cLB）可以实现对系统疾病异质性和临床前模型开发的额外分子遗传学评估。我们研究了 62 名患有各种晚期癌症类型的患者的 71 份血液样本，并将富集的循环肿瘤细胞 (CTC) 置于类器官培养条件下。 CTC 衍生的肿瘤模型通过 DNA/RNA 测序和免疫组织化学以及功能药物测试进行表征。结果与原发肿瘤、转移瘤和 CTC 的分子特征相关； CTC 计数与疾病进展相关。在来自八种不同癌症类型的 52 个 CTC 计数呈阳性 (≥1) 的样本中，只有来自两名唾液腺癌 (SGC) 患者的 CTC 形成了肿瘤样培养物 (P = 0.0005)。一名 SGC 患者的纵向 CTC 计数密切反映了治疗期间的疾病进展，并且比临床影像更早地揭示了转移复发。多组学分析和功能性体外药物测试确定了潜在的耐药机制和药物脆弱性。我们的结论是，cLB 可能会在罕见、难以治疗的癌症（例如 SGC）的个性化管理中增加功能维度（遗传方法）。© 2024 作者。约翰·威利出版的《分子肿瘤学》

While cell-free liquid biopsy (cfLB) approaches provide simple and inexpensive disease monitoring, cell-based liquid biopsy (cLB) may enable additional molecular genetic assessment of systemic disease heterogeneity and preclinical model development. We investigated 71 blood samples of 62 patients with various advanced cancer types and subjected enriched circulating tumor cells (CTCs) to organoid culture conditions. CTC-derived tumoroid models were characterized by DNA/RNA sequencing and immunohistochemistry, as well as functional drug testing. Results were linked to molecular features of primary tumors, metastases, and CTCs; CTC enumeration was linked to disease progression. Of 52 samples with positive CTC counts (≥1) from eight different cancer types, only CTCs from two salivary gland cancer (SGC) patients formed tumoroid cultures (P = 0.0005). Longitudinal CTC enumeration of one SGC patient closely reflected disease progression during treatment and revealed metastatic relapse earlier than clinical imaging. Multiomics analysis and functional in vitro drug testing identified potential resistance mechanisms and drug vulnerabilities. We conclude that cLB might add a functional dimension (to the genetic approaches) in the personalized management of rare, difficult-to-treat cancers such as SGC.© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.