TY  - JOUR
AU  - Rogers, Hazel Anne
AU  - Chapman, Rebecca
AU  - Kings, Holly
AU  - Allard, Julie
AU  - Barron-Hastings, Jodie
AU  - Pajtler, Kristian W
AU  - Sill, Martin
AU  - Pfister, Stefan
AU  - Grundy, Richard Guy
TI  - Limitations of current in vitro models for testing the clinical potential of epigenetic inhibitors for treatment of pediatric ependymoma.
JO  - OncoTarget
VL  - 9
IS  - 92
SN  - 1949-2553
CY  - [S.l.]
PB  - Impact Journals LLC
M1  - DKFZ-2019-02101
SP  - 36530-36541
PY  - 2018
AB  - Epigenetic modifications have been shown to play an important role in the classification and pathogenesis of the pediatric brain tumor ependymoma, suggesting they are a potential therapeutic target.Agents targeting epigenetic modifications inhibited the growth and induced the death of ependymoma cells with variable efficiency. However, this was often not at clinically achievable doses. Additionally, DNA methylation profiling revealed a lack of similarity to primary ependymomas suggesting alterations were induced during culture. Toxicity to fetal neural stem cells was also seen at similar drug concentrations.Agents targeting epigenetic modifications were able to inhibit the growth and induced the death of ependymoma cells grown in vitro. However, many agents were only active at high doses, outside clinical ranges, and also resulted in toxicity to normal brain cells. The lack of similarity in DNA methylation profiles between cultured cells and primary ependymomas questions the validity of using in vitro cultured cells for pre-clinical analysis of agents targeting epigenetic mechanisms and suggests further investigation using models that are more appropriate should be undertaken before agents are taken forward for clinical testing.The effects of agents targeting epigenetic modifications on the growth and death of a panel of ependymoma cell lines was investigated, as well as toxicity to normal fetal neural stem cells. The ependymoma cell lines were characterized using DNA methylation profiling.
LB  - PUB:(DE-HGF)16
C6  - pmid:30559935
C2  - pmc:PMC6284855
DO  - DOI:10.18632/oncotarget.26370
UR  - https://inrepo02.dkfz.de/record/144659
ER  -