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

Michael Poon, Morgan Bruce, Joanne Simpson, Cathal Hannan, Paul Brennan

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background: Malignant 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.
Methods: We 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).
Results: We included 212 studies from 2,789 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 24hr, 48hr and 72hr was 123.9μM (IQR 75.3-277.7μM), 223.1μM (IQR 92.0-590.1μM) and 230.0μM (IQR 34.1-650.0μM), respectively. The median IC50 at 72hr for patient-derived cell lines was 220μM (IQR 81.1-800.0μM).
Conclusion: Temozolomide 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.
Original languageEnglish
JournalBMC Cancer
DOIs
Publication statusPublished - 18 Nov 2021

Keywords / Materials (for Non-textual outputs)

  • temozolomide
  • glioma
  • preclinical
  • meta-research
  • Systematic review

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