Department of Neurosurgery, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany.
Department of Pediatric Oncology, Hematology and Clinical Immunology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Institute of Neuropathology, University Hospital Düsseldorf and Medical Faculty, Heinrich Heine University Düsseldorf, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Düsseldorf, Germany.
Biomed Pharmacother. 2021 Dec;144:112278. doi: 10.1016/j.biopha.2021.112278. Epub 2021 Oct 7.
The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation of the in vivo tumor biology and low clinical translatability. Here, we report on longitudinal epigenetic and transcriptional profiling of seven glioblastoma spheroid cell line models cultured over an extended period. Molecular profiles were associated with drug response data obtained for 231 clinically used drugs. We show that the glioblastoma spheroid models remained molecularly stable and displayed reproducible drug responses over prolonged culture times of 30 in vitro passages. Integration of gene expression and drug response data identified predictive gene signatures linked to sensitivity to specific drugs, indicating the potential of gene expression-based prediction of glioblastoma therapy response. Our data thus empowers glioblastoma spheroid disease modeling as a useful preclinical assay that may uncover novel therapeutic vulnerabilities and associated molecular alterations.
作为胶质母细胞瘤的实验模型，患者来源的肿瘤细胞系的实用性受到了挑战，因为它们对体内肿瘤生物学的代表性有限，且临床转化性低。在这里，我们报告了对七种胶质母细胞瘤球体细胞系模型进行的纵向表观遗传学和转录组学分析，这些模型在延长的培养时间内进行了培养。分子谱与为 231 种临床使用药物获得的药物反应数据相关联。我们表明，胶质母细胞瘤球体模型在长达 30 个体外传代的培养时间内保持分子稳定性，并表现出可重复的药物反应。基因表达和药物反应数据的整合确定了与特定药物敏感性相关的预测性基因特征，表明基于基因表达预测胶质母细胞瘤治疗反应的潜力。因此，我们的数据使胶质母细胞瘤球体疾病建模成为一种有用的临床前检测方法，它可能揭示新的治疗弱点和相关的分子改变。
