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

Nickel AC, Picard D, Qin N, Wolter M, Kaulich K, Hewera M, Pauck D, Marquardt V, Torga G, Muhammad S, Zhang W, Schnell O, Steiger HJ, Hänggi D, Fritsche E, Her NG, Nam DH, Carro MS, Remke M, Reifenberger G, Kahlert UD (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Biomedicine & Pharmacotherapy Elsevier Masson

Book Volume: 144

Article Number: 112278

DOI: 10.1016/j.biopha.2021.112278

Abstract

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.

Authors with CRIS profile

Oliver Schnell

Involved external institutions

Universitätsklinikum Düsseldorf DE Germany (DE) Sarah Cannon Research Institute (SCRI) US United States (USA) (US) Capital University of Medical Sciences / 首都医科大学 CN China (CN) Leibniz-Institut für umweltmedizinische Forschung (IUF) / Leibniz Research Institute for Environmental Medicine DE Germany (DE) AIMEDBIO KR Korea, Republic of (KR) Sungkyunkwan University (SKKU) KR Korea, Republic of (KR) Universitätsklinikum Freiburg DE Germany (DE)

How to cite

APA:

Nickel, A.C., Picard, D., Qin, N., Wolter, M., Kaulich, K., Hewera, M.,... Kahlert, U.D. (2021). Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses. Biomedicine & Pharmacotherapy, 144. https://doi.org/10.1016/j.biopha.2021.112278

MLA:

Nickel, A. C., et al. "Longitudinal stability of molecular alterations and drug response profiles in tumor spheroid cell lines enables reproducible analyses." Biomedicine & Pharmacotherapy 144 (2021).

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