Skip to main content
Top
Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Glioblastoma | Research article

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

Authors: Michael T. C. Poon, Morgan Bruce, Joanne E. Simpson, Cathal J. Hannan, Paul M. Brennan

Published in: BMC Cancer | Issue 1/2021

Login to get access

Abstract

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 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).

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.
Appendix
Available only for authorised users
Literature
2.
go back to reference Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013-2017. Neuro-Oncology. 2020;22:iv1–iv96.CrossRefPubMedPubMedCentral Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2013-2017. Neuro-Oncology. 2020;22:iv1–iv96.CrossRefPubMedPubMedCentral
7.
go back to reference Taslimi S, Ye VC, Zadeh G. Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 2 newly diagnosed disease. Neuro Oncol Adv. 2021;3:vdab028.CrossRef Taslimi S, Ye VC, Zadeh G. Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 2 newly diagnosed disease. Neuro Oncol Adv. 2021;3:vdab028.CrossRef
10.
go back to reference Robertson FL, Marqués-Torrejón M-A, Morrison GM, Pollard SM. Experimental models and tools to tackle glioblastoma. Dis Model Mech. 2019;12:dmm040386.CrossRefPubMedPubMedCentral Robertson FL, Marqués-Torrejón M-A, Morrison GM, Pollard SM. Experimental models and tools to tackle glioblastoma. Dis Model Mech. 2019;12:dmm040386.CrossRefPubMedPubMedCentral
12.
go back to reference Percie du Sert N, Hurst V, Ahluwalia A, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 2020;18:e3000410.CrossRefPubMedPubMedCentral Percie du Sert N, Hurst V, Ahluwalia A, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 2020;18:e3000410.CrossRefPubMedPubMedCentral
16.
go back to reference Allen M, Bjerke M, Edlund H, Nelander S, Westermark B. Origin of the U87MG glioma cell line: good news and bad news. Sci Transl Med. 2016;8:354re3.CrossRefPubMed Allen M, Bjerke M, Edlund H, Nelander S, Westermark B. Origin of the U87MG glioma cell line: good news and bad news. Sci Transl Med. 2016;8:354re3.CrossRefPubMed
21.
go back to reference Plumb JA, Milroy R, Kaye SB. Effects of the pH dependence of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-formazan absorption on chemosensitivity determined by a novel tetrazolium-based assay. Cancer Res. 1989;49(16):4435–40.PubMed Plumb JA, Milroy R, Kaye SB. Effects of the pH dependence of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-formazan absorption on chemosensitivity determined by a novel tetrazolium-based assay. Cancer Res. 1989;49(16):4435–40.PubMed
23.
go back to reference Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332.CrossRefPubMedPubMedCentral Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332.CrossRefPubMedPubMedCentral
25.
Metadata
Title
Temozolomide sensitivity of malignant glioma cell lines – a systematic review assessing consistencies between in vitro studies
Authors
Michael T. C. Poon
Morgan Bruce
Joanne E. Simpson
Cathal J. Hannan
Paul M. Brennan
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-08972-5

Other articles of this Issue 1/2021

BMC Cancer 1/2021 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine