Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses

• DOI: 10.1016/j.biopha.2021.112278
• Publication Date: 2021-10-07T15:34:05Z
• Authors: A.C. Nickel; D. Picard; N. Qin; M. Wolter; K. Kaulich; M. Hewera; D. Pauck; V. Marquardt; G. Torga; S. Muhammad; W. Zhang; O. Schnell; H.-J. Steiger; D. Hänggi; E. Fritsche; N.-G. Her; D.-H. Nam; M.S. Carro; M. Remke; G. Reifenberger; U.D. Kahlert
• Keywords: Spheroid; Drug response; U87

The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation the in vivo biology and low clinical translatability.Here, we report on longitudinal epigenetic transcriptional profiling seven spheroid line cultured over an extended period.Molecular profiles were associated with drug response data obtained 231 clinically used drugs.We show that remained molecularly stable displayed reproducible responses prolonged culture times 30 vitro passages.Integration gene expression identified predictive signatures linked to sensitivity specific drugs, indicating potential expression-based prediction therapy response.Our thus empowers disease modeling a useful preclinical assay may uncover novel therapeutic vulnerabilities molecular alterations.