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

Poon, M. T.; Bruce, M.; Simpson, J.; Hannan, C. J.; Brennan, P. M.

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 that evaluated the effect of temozolomide monotherapy on cell viability of at least one malignant glioma cell line. Studies using a drug-resistant cell line or a modified preparation of temozolomide were excluded. Key data items included type of cell lines, temozolomide exposure duration, and cell viability measure (IC50). Results: We included 212 eligible 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 cell line at 24 hours, 48 hours and 72 hours was 123.9M (IQR 75.3-277.7M), 223.1M (IQR 92.0-590.1M) and 230.0M (IQR 34.1-650.0M), respectively (Figure 2A). The median IC50 at 72 hours for patient-derived cell lines was 220M (IQR 81.1-800.0M). Conclusions: Temozolomide sensitivity reported in comparable studies was not consistent between and within individual 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.