Temozolomide sensitivity of malignant glioma cell lines – a systematic review assessing consistencies between in vitro studies

BMC Cancer

Morgan Bruce¹  Paul M. Brennan²  Michael T. C. Poon³  Joanne E. Simpson⁴  Cathal J. Hannan⁵ 

[1] Biological Sciences, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK;Cancer Research UK Brain Tumour Centre of Excellence, Edinburgh Cancer Research Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK;Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK;Cancer Research UK Brain Tumour Centre of Excellence, Edinburgh Cancer Research Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK;Centre for Medical Informatics, Usher Institute, University of Edinburgh, Nine Edinburgh BioQuarter, 9 Little France Road, Edinburgh, UK;Cancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK;Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Manchester, UK;

关键词: High grade glioma;    Glioblastoma;    Temodal;    Cell culture;    GBM;   

DOI  :  10.1186/s12885-021-08972-5

来源: Springer

【 摘 要 】

BackgroundMalignant glioma cell line models are integral to pre-clinical testing of novel potential therapies. Accurate prediction of likely efficacy in the clinic requires that these models are reliable and consistent. We assessed this by examining the reporting of experimental conditions and sensitivity to temozolomide in glioma cells lines.MethodsWe searched Medline and Embase (Jan 1994-Jan 2021) for studies evaluating the effect of temozolomide monotherapy on cell viability of at least one malignant glioma cell line. Key data items included type of cell lines, temozolomide exposure duration in hours (hr), and cell viability measure (IC50).ResultsWe included 212 studies from 2789 non-duplicate records that reported 248 distinct cell lines. The commonest cell line was U87 (60.4%). Only 10.4% studies used a patient-derived cell line. The proportion of studies not reporting each experimental condition ranged from 8.0–27.4%, including base medium (8.0%), serum supplementation (9.9%) and number of replicates (27.4%). In studies reporting IC50, the median value for U87 at 24 h, 48 h and 72 h was 123.9 μM (IQR 75.3–277.7 μM), 223.1 μM (IQR 92.0–590.1 μM) and 230.0 μM (IQR 34.1–650.0 μM), respectively. The median IC50 at 72 h for patient-derived cell lines was 220 μM (IQR 81.1–800.0 μM).ConclusionTemozolomide sensitivity reported in comparable studies was not consistent between or within malignant glioma cell lines. Drug discovery science performed on these models cannot reliably inform clinical translation. A consensus model of reporting can maximise reproducibility and consistency among in vitro studies.

【 授权许可】

CC BY